Search

Your search keyword '"Leong Jing Yao"' showing total 37 results
Start Over Author "Leong Jing Yao"
37 results on '"Leong Jing Yao"'

3. Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, van Wijk, Femke, Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, and van Wijk, Femke

Abstract

Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here, we performed CyTOF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in juvenile idiopathic arthritis (JIA). We studied different joints affected at the same time, as well as over the course of relapsing-remitting disease. We found that the composition and functional characteristics of immune infiltrates are strikingly similar between joints within one patient, and observed a strong overlap between dominant T cell clones, especially Treg, of which some could also be detected in circulation and persisted over the course of relapsing-remitting disease. Moreover, these T cell clones were characterized by a high degree of sequence similarity, indicating the presence of TCR clusters responding to the same antigens. These data suggest that in localized autoimmune disease, there is autoantigen-driven expansion of both Teffector and Treg clones that are highly persistent and are (re)circulating. These dominant clones might represent interesting therapeutic targets.

Published
2023

4. Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

Theoretical Biology and Bioinformatics, Sub Theoretical Biology, Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, van Wijk, Femke, Theoretical Biology and Bioinformatics, Sub Theoretical Biology, Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, and van Wijk, Femke

Published
2023

5. Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

CTI Van Wijk, CTI Meyaard, CDL Cluster Onderzoek en Onderwijs, CDL Cluster Speciële Diagnostiek, Cancer, Infection & Immunity, CTI Van Loosdregt, Immuno/reuma onderzoek 1 (Vastert), Immunologie/Reumatologie, Child Health, Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, van Wijk, Femke, CTI Van Wijk, CTI Meyaard, CDL Cluster Onderzoek en Onderwijs, CDL Cluster Speciële Diagnostiek, Cancer, Infection & Immunity, CTI Van Loosdregt, Immuno/reuma onderzoek 1 (Vastert), Immunologie/Reumatologie, Child Health, Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, and van Wijk, Femke

Published
2023

6. COVID-19 mRNA vaccine immunogenicity decay and breakthrough illness in adolescents and young adults with childhood-onset rheumatic diseases.

Author

Yeo, Joo Guan, Teh, Kai Liang, Chia, Wan Ni, Book, Yun Xin, Hoh, Sook Fun, Gao, Xiaocong, Das, Lena, Zhang, Jinyan, Sutamam, Nursyuhadah, Poh, Su Li, Lim, Amanda Jin Mei, Tay, Shi Huan, Yaung, Katherine Nay, Ong, Xin Mei, Leong, Jing Yao, Wang, Lin-Fa, Albani, Salvatore, and Arkachaisri, Thaschawee

Subjects
DRUG therapy for rheumatism, COVID-19, SCIENTIFIC observation, CONFIDENCE intervals, COVID-19 vaccines, ANTI-inflammatory agents, TIME, VACCINE effectiveness, DESCRIPTIVE statistics, RESEARCH funding, RHEUMATISM, VIRAL antibodies, ODDS ratio, DISEASE complications, EVALUATION, ADULTS, ADOLESCENCE
Abstract

Objectives To evaluate the humoral immunogenicity for 6 months after the two-dose coronavirus disease 2019 (COVID-19) mRNA vaccination in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs). Methods This monocentric observational study was conducted between August 2020 and March 2022. Humoral immunogenicity was assessed at 2–3 weeks after first vaccine dose and 1, 3 and 6 months after the second dose by the cPass™ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization antibody (nAb) assay. An inhibition signal of ≥30% defined the seroconversion threshold and the readings were calibrated against the World Health Organization International Standard for SARS-CoV-2 antibodies. Results. One hundred and sixty-nine AYAs with cRDs were recruited [median age 16.8 years (interquartile range, IQR 14.7–19.5), 52% female, 72% Chinese]. JIA (58%) and SLE (18%) comprised the major diagnoses. After second vaccine dose, 99% seroconverted with a median nAb titre of 1779.8 IU/ml (IQR 882.8–2541.9), declining to 935.6 IU/ml (IQR 261.0–1514.9) and 683.2 IU/ml (IQR 163.5–1400.5) at the 3- and 6-month timepoints, respectively. The diagnosis of JIA [odds ratio (OR) 10.1, 95% CI 1.8–58.4, P  = 0.010] and treatment with anti-TNF-α (aTNF) (OR 10.1, 95% CI 1.5–70.0, P  = 0.019) were independently associated with a >50% drop of nAb titres at 6 months. Withholding MTX or MMF did not affect the vaccine response or decay rate. The COVID-19 breakthrough infection was estimated at 18.2 cases/1000 patient-months with no clinical risk factors identified. Conclusion Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

7. Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

Mijnheer, Gerdien, primary, Servaas, Nila Hendrika, additional, Leong, Jing Yao, additional, Boltjes, Arjan, additional, Spierings, Eric, additional, Chen, Phyllis, additional, Lai, Liyun, additional, Petrelli, Alessandra, additional, Vastert, Sebastiaan, additional, de Boer, Rob J, additional, Albani, Salvatore, additional, Pandit, Aridaman, additional, and van Wijk, Femke, additional

Published
2023
Full Text
View/download PDF

8. Publisher Correction: The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data

Author

Yeo, Joo Guan, Wasser, Martin, Kumar, Pavanish, Pan, Lu, Poh, Su Li, Ally, Fauziah, Arkachaisri, Thaschawee, Lim, Amanda Jin Mei, Leong, Jing Yao, Lai, Liyun, Yeo, Kee Thai, Lee, Elene Seck Choon, Chua, Camillus Jian Hui, Larbi, Anis, Nyunt, Ma Shwe Zin, Ng, Tze Pin, Chiesa, Sabrina, Gattorno, Marco, Martini, Alberto, Paleja, Bhairav Suryakant, Dutertre, Charles-Antoine, Chen, Jinmiao, Nay Yaung, Katherine, Tang, Swee Ping, Ng, Sue Kheng, Yung, Chee Fu, Tan, Angela Yun June, Lee, Shu Ying, Ginhoux, Florent, and Albani, Salvatore

Published
2020
Full Text
View/download PDF

9. Author response: Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

Mijnheer, Gerdien, primary, Servaas, Nila Hendrika, primary, Leong, Jing Yao, additional, Boltjes, Arjan, additional, Spierings, Eric, additional, Chen, Phyllis, additional, Lai, Liyun, additional, Petrelli, Alessandra, additional, Vastert, Sebastiaan, additional, de Boer, Rob J, additional, Albani, Salvatore, additional, Pandit, Aridaman, additional, and van Wijk, Femke, additional

Published
2022
Full Text
View/download PDF

11. Robust neutralizing antibody response to SARS-CoV-2 mRNA vaccination in adolescents and young adults with childhood-onset rheumatic diseases

Author

Yeo, Joo Guan, primary, Chia, Wan Ni, additional, Teh, Kai Liang, additional, Book, Yun Xin, additional, Hoh, Sook Fun, additional, Gao, Xiaocong, additional, Das, Lena, additional, Zhang, Jinyan, additional, Sutamam, Nursyuhadah, additional, Lim, Amanda Jin Mei, additional, Poh, Su Li, additional, Tay, Shi Huan, additional, Nay Yaung, Katherine, additional, Ong, Xin Mei, additional, Hazirah, Sharifah Nur, additional, Chua, Camillus Jian Hui, additional, Leong, Jing Yao, additional, Wang, Lin-Fa, additional, Albani, Salvatore, additional, and Arkachaisri, Thaschawee, additional

Published
2022
Full Text
View/download PDF

12. Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

Author

Mijnheer, Gerdien, primary, Servaas, Nila Hendrika, additional, Leong, Jing Yao, additional, Boltjes, Arjan, additional, Spierings, Eric, additional, Chen, Phyllis, additional, Lai, Liyun, additional, Petrelli, Alessandra, additional, Vastert, Sebastiaan, additional, De Boer, Rob J, additional, Albani, Salvatore, additional, Pandit, Aridaman, additional, and van Wijk, Femke, additional

Published
2022
Full Text
View/download PDF

13. Reply to Over-celling fetal microbial exposure

Author

Martin Wasser, Florent Ginhoux, Leong Jing Yao, Jerry Kok Yen Chan, Costerwell Khyriem, Archita Mishra, Naomi McGovern, Salvatore Albani, and Benoit Malleret

Subjects
Fetus, MEDLINE, Physiology, Biology, General Biochemistry, Genetics and Molecular Biology
Published
2021

14. Microbial exposure during early human development primes fetal immune cells

Author

Leong Jing Yao, Ravid Straussman, Avery Khoo May Lee, Kalyani Srinivasan, Gurmit Singh Naranjan Singh, David Vermijlen, Fabien Cottier, Nurhidaya Binte Shadan, Costerwell Khyriem, Gillian Low, Garold Fuks, Mahesh Choolani, Noam Shental, Salvatore Albani, Xiao Meng Zhang, Thet Tun Aung, Rhea Pai, Charles-Antoine Dutertre, Aviva Rotter-Maskowitz, Benoit Malleret, Archita Mishra, Svetoslav Chakarov, Adhika Shanti, Ghee Chuan Lai, Naomi McGovern, Regina Men Men Wong, Jerry Kok Yen Chan, Edwin Shepherdson, Alrina Shin Min Tan, Andrea Lee, Ankur Sharma, Pei Xiang Hor, Florent Ginhoux, Yiping Fan, Norman Pavelka, Shabnam Khalilnezhad, Phyllis Chen, McGovern, Naomi [0000-0001-5200-2698], and Apollo - University of Cambridge Repository

Subjects
Adult, immune priming, T-Lymphocytes, Bactériologie médicale, microbiome, Embryonic Development, Biology, medicine.disease_cause, fetal Development, Lymphocyte Activation, immune memory, General Biochemistry, Genetics and Molecular Biology, Andrology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Fetus, Pregnancy, Placenta, RNA, Ribosomal, 16S, Immunologie, medicine, Leukocytes, Humans, Microbiome, bacteria, Lymph node, 030304 developmental biology, Cell Proliferation, 0303 health sciences, Microbial Viability, Reproducibility of Results, Dendritic Cells, fetal immunity, Treg, Gastrointestinal Tract, RNA, Bacterial, medicine.anatomical_structure, In utero, Pregnancy Trimester, Second, embryonic structures, Tem, Gestation, Female, microbes, Staphylococcus, Immunologic Memory, 030217 neurology & neurosurgery
Abstract

Summary The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

Published
2021
Full Text
View/download PDF

15. A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19

Author

Yeo, Joo Guan, primary, Leong, Jing Yao, additional, Tay, Shi Huan, additional, Nadua, Karen Donceras, additional, Anderson, Danielle E., additional, Lim, Amanda Jin Mei, additional, Ng, Xiang Wen, additional, Poh, Su Li, additional, Guo, Dianyan, additional, Yaung, Katherine Nay, additional, Kumar, Pavanish, additional, Wasser, Martin, additional, Hazirah, Sharifah Nur, additional, Sutamam, Nursyuhadah, additional, Chua, Camillus Jian Hui, additional, Qui, Martin, additional, Foo, Randy, additional, Gamage, Akshamal Mihiranga, additional, Yeo, Kee Thai, additional, Ramakrishna, Lakshmi, additional, Arkachaisri, Thaschawee, additional, Young, Barnaby E., additional, Lye, David Chien, additional, Wang, Lin-Fa, additional, Chong, Chia Yin, additional, Tan, Natalie Woon Hui, additional, Li, Jiahui, additional, Kam, Kai-Qian, additional, Ginhoux, Florent, additional, Thoon, Koh Cheng, additional, Chan, Jerry Kok Yen, additional, Yung, Chee Fu, additional, and Albani, Salvatore, additional

Published
2021
Full Text
View/download PDF

17. Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis

Author

Leong Jing Yao, Jorg van Loosdregt, Salvatore Albani, Gary W. Williams, Camillus Chua, Ken D. Pischel, Alberto Martini, Marco Gattorno, Thaschawee Arkachaisri, Martin Lotz, Alessandro Consolaro, Pavanish Kumar, Suzan Saidin, and Bhairav Paleja

Subjects
CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Regulator, Arthritis, MYC, Jurkat cells, Arthritis, Rheumatoid, Pathogenesis, Jurkat Cells, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, Gene Regulatory Networks, Oxadiazoles, Pathogenic T cells, High-Throughput Nucleotide Sequencing, medicine.anatomical_structure, Mice, Inbred DBA, Female, medicine.symptom, Adult, Adolescent, T cell, Primary Cell Culture, Immunology, Inflammation, Biology, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Autophagy, medicine, Animals, Humans, Rheumatoid arthritis, Autophagic memory, DNA Methylation, medicine.disease, Arthritis, Juvenile, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Cancer research, Immunologic Memory, Memory T cell, 030217 neurology & neurosurgery, Transcription Factors
Abstract

T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis. We demonstrated "Autophagic memory" as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased autophagy. The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target.

Published
2018

18. The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data

Author

Yeo, Joo Guan, primary, Wasser, Martin, additional, Kumar, Pavanish, additional, Pan, Lu, additional, Poh, Su Li, additional, Ally, Fauziah, additional, Arkachaisri, Thaschawee, additional, Lim, Amanda Jin Mei, additional, Leong, Jing Yao, additional, Lai, Liyun, additional, Yeo, Kee Thai, additional, Lee, Elene Seck Choon, additional, Chua, Camillus Jian Hui, additional, Larbi, Anis, additional, Nyunt, Ma Shwe Zin, additional, Ng, Tze Pin, additional, Chiesa, Sabrina, additional, Gattorno, Marco, additional, Martini, Alberto, additional, Paleja, Bhairav Suryakant, additional, Dutertre, Charles-Antoine, additional, Chen, Jinmiao, additional, Nay Yaung, Katherine, additional, Tang, Swee Ping, additional, Ng, Sue Kheng, additional, Yung, Chee Fu, additional, Tan, Angela Yun June, additional, Lee, Shu Ying, additional, Ginhoux, Florent, additional, and Albani, Salvatore, additional

Published
2020
Full Text
View/download PDF

19. The EPIC data analytics platform for clinical mass cytometry

Author

Wasser, Martin, primary, Yeo, Joo Guan, additional, Kumar, Pavanish, additional, Chew, Valerie, additional, Lim, Chun Jye, additional, Arkachaisri, Thaschawee, additional, Poh, Su Li, additional, Leong, Jing Yao, additional, Yeo, Kee Thai, additional, and Albani, Salvatore, additional

Published
2020
Full Text
View/download PDF

20. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Author

Dutertre, Charles Antoine, Becht, Etienne, Irac, Sergio Erdal, Khalilnezhad, Ahad, Narang, Vipin, Khalilnezhad, Shabnam, Ng, Pei Y., van den Hoogen, Lucas L., Leong, Jing Yao, Lee, Bernett, Chevrier, Marion, Zhang, Xiao Meng, Yong, Pearly Jean Ai, Koh, Geraldine, Lum, Josephine, Howland, Shanshan Wu, Mok, Esther, Chen, Jinmiao, Larbi, Anis, Tan, Henry Kun Kiaang, Lim, Tony Kiat Hon, Karagianni, Panagiota, Tzioufas, Athanasios G., Malleret, Benoit, Brody, Joshua, Albani, Salvatore, van Roon, Joel, Radstake, Timothy, Newell, Evan W., Ginhoux, Florent, Dutertre, Charles Antoine, Becht, Etienne, Irac, Sergio Erdal, Khalilnezhad, Ahad, Narang, Vipin, Khalilnezhad, Shabnam, Ng, Pei Y., van den Hoogen, Lucas L., Leong, Jing Yao, Lee, Bernett, Chevrier, Marion, Zhang, Xiao Meng, Yong, Pearly Jean Ai, Koh, Geraldine, Lum, Josephine, Howland, Shanshan Wu, Mok, Esther, Chen, Jinmiao, Larbi, Anis, Tan, Henry Kun Kiaang, Lim, Tony Kiat Hon, Karagianni, Panagiota, Tzioufas, Athanasios G., Malleret, Benoit, Brody, Joshua, Albani, Salvatore, van Roon, Joel, Radstake, Timothy, Newell, Evan W., and Ginhoux, Florent

Published
2019

21. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Author

UMC Utrecht, Translationele immunologie, Infection & Immunity, CTI Radstake, Dutertre, Charles Antoine, Becht, Etienne, Irac, Sergio Erdal, Khalilnezhad, Ahad, Narang, Vipin, Khalilnezhad, Shabnam, Ng, Pei Y., van den Hoogen, Lucas L., Leong, Jing Yao, Lee, Bernett, Chevrier, Marion, Zhang, Xiao Meng, Yong, Pearly Jean Ai, Koh, Geraldine, Lum, Josephine, Howland, Shanshan Wu, Mok, Esther, Chen, Jinmiao, Larbi, Anis, Tan, Henry Kun Kiaang, Lim, Tony Kiat Hon, Karagianni, Panagiota, Tzioufas, Athanasios G., Malleret, Benoit, Brody, Joshua, Albani, Salvatore, van Roon, Joel, Radstake, Timothy, Newell, Evan W., Ginhoux, Florent, UMC Utrecht, Translationele immunologie, Infection & Immunity, CTI Radstake, Dutertre, Charles Antoine, Becht, Etienne, Irac, Sergio Erdal, Khalilnezhad, Ahad, Narang, Vipin, Khalilnezhad, Shabnam, Ng, Pei Y., van den Hoogen, Lucas L., Leong, Jing Yao, Lee, Bernett, Chevrier, Marion, Zhang, Xiao Meng, Yong, Pearly Jean Ai, Koh, Geraldine, Lum, Josephine, Howland, Shanshan Wu, Mok, Esther, Chen, Jinmiao, Larbi, Anis, Tan, Henry Kun Kiaang, Lim, Tony Kiat Hon, Karagianni, Panagiota, Tzioufas, Athanasios G., Malleret, Benoit, Brody, Joshua, Albani, Salvatore, van Roon, Joel, Radstake, Timothy, Newell, Evan W., and Ginhoux, Florent

Published
2019

22. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2

Author

Yie Hou Lee, Donovan Low, Yiping Fan, Nurhidaya Binte Shadan, Edwin Huang Kunxiang, Venetia Bigley, Sandra Hubert, Dedrick Kok Hong Chan, Matthew Collin, Anis Larbi, Gillian Low, John Kit Chung Tam, Peter See, Michael Poidinger, Erin Soon, Kaibo Duan, Citra Nurfarah Zaini Mattar, Mahesh Choolani, Esther Wing Hei Mok, Muzlifah Haniffa, Salvatore Albani, Christopher Schuster, Jerry Kok Yen Chan, Baptiste Janela, Naomi McGovern, Florent Ginhoux, Xiao-Nong Wang, Tony Kiat Hon Lim, Evan W. Newell, Rasha Msallam, Leong Jing Yao, Adelheid Elbe-Bürger, Josephine Lum, Ivy Low, Hermi Sumatoh, Andreas Schlitzer, Amanda Shin, Ker-Kan Tan, McGovern, Naomi [0000-0001-5200-2698], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, immunology [Dendritic Cells], T-Lymphocytes, T-Lymphocytes, Regulatory, immunology [T-Lymphocytes], Immune tolerance, 0302 clinical medicine, metabolism [Arginase], Cell Movement, Receptor, enzymology [Fetus], Multidisciplinary, Toll-Like Receptors, cytology [Fetus], medicine.anatomical_structure, cytology [T-Lymphocytes, Regulatory], Cytokines, ddc:500, cytology [Lymph Nodes], immunology [T-Lymphocytes, Regulatory], Adult, cytology [T-Lymphocytes], T cell, arginase II, human, Article, 03 medical and health sciences, Immune system, Fetus, Antigen, Immunity, medicine, Immune Tolerance, Humans, immunology [Lymph Nodes], Cell Proliferation, enzymology [Dendritic Cells], Arginase, biosynthesis [Cytokines], immunology [Fetus], Dendrites, Dendritic Cells, 030104 developmental biology, immunology [Toll-Like Receptors], immunology [Cytokines], Immunology, Lymph Nodes, Homeostasis, 030215 immunology
Abstract

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

Published
2018
Full Text
View/download PDF

24. Immunome perturbation is present in patients with juvenile idiopathic arthritis who are in remission and will relapse upon anti-TNFα withdrawal

Author

Leong, Jing Yao, primary, Chen, Phyllis, additional, Yeo, Joo Guan, additional, Ally, Fauziah, additional, Chua, Camillus, additional, Nur Hazirah, Sharifah, additional, Poh, Su Li, additional, Pan, Lu, additional, Lai, Liyun, additional, Lee, Elene Seck Choon, additional, Bathi, Loshinidevi D/O Thana, additional, Arkachaisri, Thaschawee, additional, Lovell, Daniel, additional, and Albani, Salvatore, additional

Published
2019
Full Text
View/download PDF

25. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Author

Dutertre, Charles-Antoine, primary, Becht, Etienne, additional, Irac, Sergio Erdal, additional, Khalilnezhad, Ahad, additional, Narang, Vipin, additional, Khalilnezhad, Shabnam, additional, Ng, Pei Y., additional, van den Hoogen, Lucas L., additional, Leong, Jing Yao, additional, Lee, Bernett, additional, Chevrier, Marion, additional, Zhang, Xiao Meng, additional, Yong, Pearly Jean Ai, additional, Koh, Geraldine, additional, Lum, Josephine, additional, Howland, Shanshan Wu, additional, Mok, Esther, additional, Chen, Jinmiao, additional, Larbi, Anis, additional, Tan, Henry Kun Kiaang, additional, Lim, Tony Kiat Hon, additional, Karagianni, Panagiota, additional, Tzioufas, Athanasios G., additional, Malleret, Benoit, additional, Brody, Joshua, additional, Albani, Salvatore, additional, van Roon, Joel, additional, Radstake, Timothy, additional, Newell, Evan W., additional, and Ginhoux, Florent, additional

Published
2019
Full Text
View/download PDF

26. SAT0024 TRANSCRIPTOMIC PROFILING OF THE MICROENVIRONMENT DRIVEN RE-SHAPING OF PATHOGENIC CIRCULATORY AND SYNOVIAL HLA-DR+ CD4 T SUBSETS IN ACTIVE JUVENILE IDIOPATHIC ARTHRITIC PATIENTS

Author

Leong, Jing yao, primary, Kumar, Pavanish, additional, Chen, Phyllis, additional, Yeo, Joo Guan, additional, Chua, Camillus, additional, Hazirah, Sharifah Nur, additional, Arkachaisri, Thaschawee, additional, Consolaro, Alessandro, additional, Gattorno, Marco, additional, Martini, Alberto, additional, and Albani, Salvatore, additional

Published
2019
Full Text
View/download PDF

27. AB1190 EXTENDED POLY-DIMENSIONAL IMMUNOME CHARACTERIZATION (EPIC): A WEB-BASED IMMUNE REFERENCE ATLAS OF THE HEALTHY HUMAN IMMUNOME AND A TOOL FOR TRANSLATIONAL MEDICINE

Author

Yeo, Joo Guan, primary, Pan, Lu, additional, Wasser, Martin, additional, Kumar, Pavanish, additional, Arkachaisri, Thaschawee, additional, Poh, Su LI, additional, Ally, Fauziah, additional, Leong, Jing Yao, additional, Yeo, Kee Thai, additional, Lai, Liyun, additional, June Tan, Angela Yun, additional, and Albani, Salvatore, additional

Published
2019
Full Text
View/download PDF

30. Immunome perturbation is present in patients with juvenile idiopathic arthritis who are in remission and will relapse upon anti-TNFα withdrawal.

Author

Jing Yao Leong, Chen, Phyllis, Joo Guan Yeo, Ally, Fauziah, Chua, Camillus, Hazirah, Sharifah Nur, Su Li Poh, Lu Pan, Liyun Lai, Choon Lee, Elene Seck, Loshinidevi, Arkachaisri, Thaschawee, Lovell, Daniel, Albani, Salvatore, Leong, Jing Yao, Yeo, Joo Guan, Nur Hazirah, Sharifah, Poh, Su Li, Pan, Lu, and Lai, Liyun

Subjects
BIOTHERAPY, RESEARCH, RESEARCH methodology, JUVENILE idiopathic arthritis, EVALUATION research, MEDICAL cooperation, DISEASE relapse, COMPARATIVE studies, TUMOR necrosis factors, T cells, CELLULAR immunity, DISEASE remission, PASSIVE euthanasia, LONGITUDINAL method, CHEMICAL inhibitors
Abstract

Objectives: Biologics treatment with antitumour necrosis factor alpha (TNFα) is efficacious in patients with juvenile idiopathic arthritis (JIA). Despite displaying clinical inactivity during treatment, many patients will flare on cessation of therapy. The inability to definitively discriminate patients who will relapse or continue to remain in remission after therapy withdrawal is currently a major unmet medical need. CD4 T cells have been implicated in active disease, yet how they contribute to disease persistence despite treatment is unknown.Methods: We interrogated the circulatory reservoir of CD4+ immune subsets at the single-cell resolution with mass cytometry (cytometry by time of flight) of patients with JIA (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission. These patients were examined prior to therapy withdrawal for putative subsets that could discriminate relapse from remission. We verified on a separate JIA cohort (n=16) the dysregulation of these circulatory subsets 8 months into therapy withdrawal. The immunological transcriptomic signature of CD4 memory in relapse/remission patients was examined with NanoString.Results: An inflammatory memory subset of CD3+CD4+CD45RA-TNFα+ T cells deficient in immune checkpoints (PD1-CD152-) was present in relapse patients prior to therapy withdrawal. Transcriptomic profiling reveals divergence between relapse and remission patients in disease-centric pathways involving (1) T-cell receptor activation, (2) apoptosis, (3) TNFα, (4) nuclear factor-kappa B and (5) mitogen-activated protein kinase signalling.Conclusions: A unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

32. Ex vivo-expanded, but not in vitro-induced, human regulatory T cells are candidates for cell therapy in autoimmune diseases due to stable demethylation of the FOXP3 TSDRa

Author

Rossetti, Maura, Spreafico, Roberto, Saidin, Suzan, Chua, Camillus, Moshref, Maryam, Leong, Jing Yao, Tan, York Kiat, Thumboo, Julian, van Loosdregt, Jorg, and Albani, Salvatore

Subjects
Adult, Male, Cell- and Tissue-Based Therapy, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, Arthritis, Rheumatoid, Mice, Transforming Growth Factor beta, Animals, Humans, CTLA-4 Antigen, Cells, Cultured, Aged, Cell Proliferation, Sirolimus, Tumor Necrosis Factor-alpha, Interleukins, hemic and immune systems, Forkhead Transcription Factors, DNA Methylation, Middle Aged, Interleukin-10, Female, Immunosuppressive Agents
Abstract

Regulatory T cell (Treg) therapy is a promising approach for transplant rejection and severe autoimmunity. Unfortunately, clinically meaningful Treg numbers can be obtained only upon in vitro culture. Functional stability of human expanded (e)Tregs and induced (i)Tregs has not been thoroughly addressed for all proposed protocols, hindering clinical translation. We undertook a systematic comparison of eTregs and iTregs to recommend the most suitable for clinical implementation, and then tested their effectiveness and feasibility in rheumatoid arthritis (RA). Regardless of the treatment, iTregs acquired suppressive function and FOXP3 expression, but lost them upon secondary restimulation in the absence of differentiation factors, which mimics in vivo reactivation. In contrast, eTregs expanded in the presence of rapamycin (rapa) retained their regulatory properties and FOXP3 demethylation upon restimulation with no stabilizing agent. FOXP3 demethylation predicted Treg functional stability upon secondary TCR engagement. Rapa eTregs suppressed conventional T cell proliferation via both surface (CTLA-4) and secreted (IL-10, TGF-β, and IL-35) mediators, similarly to ex vivo Tregs. Importantly, Treg expansion with rapa from RA patients produced functionally stable Tregs with yields comparable to healthy donors. Moreover, rapa eTregs from RA patients were resistant to suppression reversal by the proinflammatory cytokine TNF-α, and were more efficient in suppressing synovial conventional T cell proliferation compared with their ex vivo counterparts, suggesting that rapa improves both Treg function and stability. In conclusion, our data indicate Treg expansion with rapa as the protocol of choice for clinical application in rheumatological settings, with assessment of FOXP3 demethylation as a necessary quality control step.

Published
2014

33. TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis

Author

Rossetti, Maura, primary, Spreafico, Roberto, additional, Consolaro, Alessandro, additional, Leong, Jing Yao, additional, Chua, Camillus, additional, Massa, Margherita, additional, Saidin, Suzan, additional, Magni-Manzoni, Silvia, additional, Arkachaisri, Thaschawee, additional, Wallace, Carol A, additional, Gattorno, Marco, additional, Martini, Alberto, additional, Lovell, Daniel J, additional, and Albani, Salvatore, additional

Published
2016
Full Text
View/download PDF

35. Ex vivo-expanded but not in vitro-induced human regulatory T cells are candidates for cell therapy in autoimmune diseases thanks to stable demethylation of the FOXP3 regulatory T cell-specific demethylated region

Author

Rossetti, Maura, Spreafico, Roberto, Saidin, Suzan, Chua, Camillus, Moshref, Maryam, Leong, Jing Yao, Tan, York Kiat, Thumboo, Julian, van Loosdregt, Jorg, Albani, Salvatore, Rossetti, Maura, Spreafico, Roberto, Saidin, Suzan, Chua, Camillus, Moshref, Maryam, Leong, Jing Yao, Tan, York Kiat, Thumboo, Julian, van Loosdregt, Jorg, and Albani, Salvatore

Published
2015

36. Ex vivo-expanded but not in vitro-induced human regulatory T cells are candidates for cell therapy in autoimmune diseases thanks to stable demethylation of the FOXP3 regulatory T cell-specific demethylated region

Author

Immunologie onderzoek 2, Child Health, Infection & Immunity, Rossetti, Maura, Spreafico, Roberto, Saidin, Suzan, Chua, Camillus, Moshref, Maryam, Leong, Jing Yao, Tan, York Kiat, Thumboo, Julian, van Loosdregt, Jorg, Albani, Salvatore, Immunologie onderzoek 2, Child Health, Infection & Immunity, Rossetti, Maura, Spreafico, Roberto, Saidin, Suzan, Chua, Camillus, Moshref, Maryam, Leong, Jing Yao, Tan, York Kiat, Thumboo, Julian, van Loosdregt, Jorg, and Albani, Salvatore

Published
2015

37. Ex Vivo–Expanded but Not In Vitro–Induced Human Regulatory T Cells Are Candidates for Cell Therapy in Autoimmune Diseases Thanks to Stable Demethylation of the FOXP3 Regulatory T Cell–Specific Demethylated Region

Author

Rossetti, Maura, primary, Spreafico, Roberto, additional, Saidin, Suzan, additional, Chua, Camillus, additional, Moshref, Maryam, additional, Leong, Jing Yao, additional, Tan, York Kiat, additional, Thumboo, Julian, additional, van Loosdregt, Jorg, additional, and Albani, Salvatore, additional

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results