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29 results on '"Balachander, Akhila"'

1. iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer

Author

Park, Dong Shin, Kozaki, Tatsuya, Tiwari, Satish Kumar, Moreira, Marco, Khalilnezhad, Ahad, Torta, Federico, Olivié, Nicolas, Thiam, Chung Hwee, Liani, Oniko, Silvin, Aymeric, Phoo, Wint Wint, Gao, Liang, Triebl, Alexander, Tham, Wai Kin, Gonçalves, Leticia, Kong, Wan Ting, Raman, Sethi, Zhang, Xiao Meng, Dunsmore, Garett, Dutertre, Charles Antoine, Lee, Salanne, Ong, Jia Min, Balachander, Akhila, Khalilnezhad, Shabnam, Lum, Josephine, Duan, Kaibo, Lim, Ze Ming, Tan, Leonard, Low, Ivy, Utami, Kagistia Hana, Yeo, Xin Yi, Di Tommaso, Sylvaine, Dupuy, Jean-William, Varga, Balazs, Karadottir, Ragnhildur Thora, Madathummal, Mufeeda Changaramvally, Bonne, Isabelle, Malleret, Benoit, Binte, Zainab Yasin, Wei Da, Ngan, Tan, Yingrou, Wong, Wei Jie, Zhang, Jinqiu, Chen, Jinmiao, Sobota, Radoslaw M., Howland, Shanshan W., Ng, Lai Guan, Saltel, Frédéric, Castel, David, Grill, Jacques, Minard, Veronique, Albani, Salvatore, Chan, Jerry K. Y., Thion, Morgane Sonia, Jung, Sang Yong, Wenk, Markus R., Pouladi, Mahmoud A., Pasqualini, Claudia, Angeli, Veronique, Cexus, Olivier N. F., and Ginhoux, Florent

Published
2023
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2. CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses

Author

Chong, Shu Zhen, Evrard, Maximilien, Devi, Sapna, Chen, Jinmiao, Lim, Jyue Yuan, See, Peter, Zhang, Yiru, Adrover, José M, Lee, Bernett, Tan, Leonard, Li, Jackson LY, Liong, Ka Hang, Phua, Cindy, Balachander, Akhila, Boey, Adrian, Liebl, David, Tan, Suet Mien, Chan, Jerry KY, Balabanian, Karl, Harris, John E, Bianchini, Mariaelvy, Weber, Christian, Duchene, Johan, Lum, Josephine, Poidinger, Michael, Chen, Qingfeng, Rénia, Laurent, Wang, Cheng-I, Larbi, Anis, Randolph, Gwendalyn J, Weninger, Wolfgang, Looney, Mark R, Krummel, Matthew F, Biswas, Subhra K, Ginhoux, Florent, Hidalgo, Andrés, Bachelerie, Françoise, and Ng, Lai Guan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Good Health and Well Being, Animals, Antigens, Ly, Bone Marrow Cells, Cell Differentiation, Circadian Rhythm, Endotoxins, Female, Gene Expression Profiling, Lung, Mice, Inbred C57BL, Monocytes, Receptors, CXCR4, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.

Published
2016

4. Mitochondrial Dysfunction in CD4+ T Effector Memory RA+ Cells

Author

Strickland, Marie, primary, Lee, Salanne, additional, Neo, Shi Yong, additional, Balachander, Akhila, additional, Low, Ivy, additional, Mustafah, Seri, additional, Ing, Goh Wah, additional, Wright, Graham D., additional, Larbi, Anis, additional, and Pender, Sylvia L. F., additional

Published
2023
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8. Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis

Author

Cheng, Catherine Y., Gutierrez, Nuria M., Marzuki, Mardiana B., Lu, Xiaohua, Foreman, Taylor W., Paleja, Bhairav, Lee, Bernett, Balachander, Akhila, Chen, Jinmiao, Tsenova, Liana, Kurepina, Natalia, Teng, Karen W. W., West, Kim, Mehra, Smriti, Zolezzi, Francesca, Poidinger, Michael, Kreiswirth, Barry, Kaushal, Deepak, Kornfeld, Hardy, Newell, Evan W., and Singhal, Amit

Published
2017
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9. Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration

Author

Silvin, Aymeric, primary, Uderhardt, Stefan, additional, Piot, Cecile, additional, Da Mesquita, Sandro, additional, Yang, Katharine, additional, Geirsdottir, Laufey, additional, Mulder, Kevin, additional, Eyal, David, additional, Liu, Zhaoyuan, additional, Bridlance, Cecile, additional, Thion, Morgane Sonia, additional, Zhang, Xiao Meng, additional, Kong, Wan Ting, additional, Deloger, Marc, additional, Fontes, Vasco, additional, Weiner, Assaf, additional, Ee, Rachel, additional, Dress, Regine, additional, Hang, Jing Wen, additional, Balachander, Akhila, additional, Chakarov, Svetoslav, additional, Malleret, Benoit, additional, Dunsmore, Garett, additional, Cexus, Olivier, additional, Chen, Jinmiao, additional, Garel, Sonia, additional, Dutertre, Charles Antoine, additional, Amit, Ido, additional, Kipnis, Jonathan, additional, and Ginhoux, Florent, additional

Published
2022
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10. A phase 1b study of OXIRI in pancreatic adenocarcinoma patients and its immunomodulatory effects

Author

Ng, Matthew, primary, Chen, Sylvia, additional, Ong, Whee Sze, additional, Balachander, Akhila, additional, Seet, Amanda, additional, Yeong, Joe, additional, Sutiman, Natalia, additional, Lim, Tony Kiat Hon, additional, Lee, Bernett, additional, Guo, Yu Amanda, additional, Leong, Wai Fook, additional, Lee, Sze Sing, additional, Lam, Justina, additional, Choo, Su Pin, additional, Skanderup, Anders Jacobsen, additional, Biswas, Subhra Kumar, additional, Tai, David, additional, and Chowbay, Balram, additional

Published
2022
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12. A subset of Kupffer cells regulates metabolism through the expression of CD36

Author

Blériot, Camille, primary, Barreby, Emelie, additional, Dunsmore, Garett, additional, Ballaire, Raphaelle, additional, Chakarov, Svetoslav, additional, Ficht, Xenia, additional, De Simone, Giorgia, additional, Andreata, Francesco, additional, Fumagalli, Valeria, additional, Guo, Wei, additional, Wan, Guochen, additional, Gessain, Gregoire, additional, Khalilnezhad, Ahad, additional, Zhang, Xiao Meng, additional, Ang, Nicholas, additional, Chen, Ping, additional, Morgantini, Cecilia, additional, Azzimato, Valerio, additional, Kong, Wan Ting, additional, Liu, Zhaoyuan, additional, Pai, Rhea, additional, Lum, Josephine, additional, Shihui, Foo, additional, Low, Ivy, additional, Xu, Connie, additional, Malleret, Benoit, additional, Kairi, Muhammad Faris Mohd, additional, Balachander, Akhila, additional, Cexus, Olivier, additional, Larbi, Anis, additional, Lee, Bernett, additional, Newell, Evan W., additional, Ng, Lai Guan, additional, Phoo, Wint Wint, additional, Sobota, Radoslaw M., additional, Sharma, Ankur, additional, Howland, Shanshan W., additional, Chen, Jinmiao, additional, Bajenoff, Marc, additional, Yvan-Charvet, Laurent, additional, Venteclef, Nicolas, additional, Iannacone, Matteo, additional, Aouadi, Myriam, additional, and Ginhoux, Florent, additional

Published
2021
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14. A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart

Author

Ministerio de Economía y Competitividad (España), European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Fondation Leducq, Comunidad de Madrid, La Caixa, Fundació La Marató de TV3, Fundación la Caixa, Howard Hughes Medical Institute, Centro Nacional de Investigaciones Cardiovasculares (España), Nicolás-Ávila, José A., Lechuga, Ana, Sanchez-Díaz, María, Díaz-García, Elena, Santiago, Demetrio J., Rubio-Ponce, Andrea, LiangYao Li, Jackson, Balachander, Akhila, Quintana, Juan A., Martínez de Mena, Raquel, Castejón-Vega, Beatriz, Pun-García, Andrés, Través, Paqui G., Bonzón-Kulichenko, Elena, García-Marqués, Fernando, Cussó, Lorena, González, Noelia A., González-Guerra, Andrés, Roche-Molina, Marta, Martin-Salamanca, Sandra, Crainiciuc, Georgiana, Guzmán, Gabriela, Larrazabal, Jagoba, Herrero-Galán, Elías, Alegre-Cebollada, Jorge, Lemke, Greg, Rothlin, Carla V., Jiménez-Borreguero, Luis J., Reyes, Guillermo, Castrillo, Antonio, Desco, Manuel, Muñoz-Cánoves, Pura, Ibáñez, Borja, Torres, Miguel, Guan Ng, Lai, Priori, Silvia G., Bueno, Héctor, Vázquez, Jesús, Cordero, Mario D., Bernal, Juan, Enríquez, José Antonio, Hidalgo, Andrés, Ministerio de Economía y Competitividad (España), European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Fondation Leducq, Comunidad de Madrid, La Caixa, Fundació La Marató de TV3, Fundación la Caixa, Howard Hughes Medical Institute, Centro Nacional de Investigaciones Cardiovasculares (España), Nicolás-Ávila, José A., Lechuga, Ana, Sanchez-Díaz, María, Díaz-García, Elena, Santiago, Demetrio J., Rubio-Ponce, Andrea, LiangYao Li, Jackson, Balachander, Akhila, Quintana, Juan A., Martínez de Mena, Raquel, Castejón-Vega, Beatriz, Pun-García, Andrés, Través, Paqui G., Bonzón-Kulichenko, Elena, García-Marqués, Fernando, Cussó, Lorena, González, Noelia A., González-Guerra, Andrés, Roche-Molina, Marta, Martin-Salamanca, Sandra, Crainiciuc, Georgiana, Guzmán, Gabriela, Larrazabal, Jagoba, Herrero-Galán, Elías, Alegre-Cebollada, Jorge, Lemke, Greg, Rothlin, Carla V., Jiménez-Borreguero, Luis J., Reyes, Guillermo, Castrillo, Antonio, Desco, Manuel, Muñoz-Cánoves, Pura, Ibáñez, Borja, Torres, Miguel, Guan Ng, Lai, Priori, Silvia G., Bueno, Héctor, Vázquez, Jesús, Cordero, Mario D., Bernal, Juan, Enríquez, José Antonio, and Hidalgo, Andrés

Abstract

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. Video Abstract: [Figure presented] A system of macrophages in the heart supports cardiomyocyte health by phagocytosing exopher particles ejected from cardiomyocytes that contain defective mitochondria, among other cellular contents.

Published
2020

15. Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe

Author

Yeo, Kim Pin, primary, Lim, Hwee Ying, additional, Thiam, Chung Hwee, additional, Azhar, Syaza Hazwany, additional, Tan, Caris, additional, Tang, Ya, additional, See, Wei Qiang, additional, Koh, Xuan Han, additional, Zhao, Ming Hao, additional, Phua, Meow Ling, additional, Balachander, Akhila, additional, Tan, Yingrou, additional, Lim, Sheau Yng, additional, Chew, Hui Shang, additional, Ng, Lai Guan, additional, and Angeli, Veronique, additional

Published
2020
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16. A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart

Author

Nicolás-Ávila, José A., primary, Lechuga-Vieco, Ana V., additional, Esteban-Martínez, Lorena, additional, Sánchez-Díaz, María, additional, Díaz-García, Elena, additional, Santiago, Demetrio J., additional, Rubio-Ponce, Andrea, additional, Li, Jackson LiangYao, additional, Balachander, Akhila, additional, Quintana, Juan A., additional, Martínez-de-Mena, Raquel, additional, Castejón-Vega, Beatriz, additional, Pun-García, Andrés, additional, Través, Paqui G., additional, Bonzón-Kulichenko, Elena, additional, García-Marqués, Fernando, additional, Cussó, Lorena, additional, A-González, Noelia, additional, González-Guerra, Andrés, additional, Roche-Molina, Marta, additional, Martin-Salamanca, Sandra, additional, Crainiciuc, Georgiana, additional, Guzmán, Gabriela, additional, Larrazabal, Jagoba, additional, Herrero-Galán, Elías, additional, Alegre-Cebollada, Jorge, additional, Lemke, Greg, additional, Rothlin, Carla V., additional, Jimenez-Borreguero, Luis Jesús, additional, Reyes, Guillermo, additional, Castrillo, Antonio, additional, Desco, Manuel, additional, Muñoz-Cánoves, Pura, additional, Ibáñez, Borja, additional, Torres, Miguel, additional, Ng, Lai Guan, additional, Priori, Silvia G., additional, Bueno, Héctor, additional, Vázquez, Jesús, additional, Cordero, Mario D., additional, Bernal, Juan A., additional, Enríquez, José A., additional, and Hidalgo, Andrés, additional

Published
2020
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17. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches

Author

Chakarov, Svetoslav, primary, Lim, Hwee Ying, additional, Tan, Leonard, additional, Lim, Sheau Yng, additional, See, Peter, additional, Lum, Josephine, additional, Zhang, Xiao-Meng, additional, Foo, Shihui, additional, Nakamizo, Satoshi, additional, Duan, Kaibo, additional, Kong, Wan Ting, additional, Gentek, Rebecca, additional, Balachander, Akhila, additional, Carbajo, Daniel, additional, Bleriot, Camille, additional, Malleret, Benoit, additional, Tam, John Kit Chung, additional, Baig, Sonia, additional, Shabeer, Muhammad, additional, Toh, Sue-Anne Ee Shiow, additional, Schlitzer, Andreas, additional, Larbi, Anis, additional, Marichal, Thomas, additional, Malissen, Bernard, additional, Chen, Jinmiao, additional, Poidinger, Michael, additional, Kabashima, Kenji, additional, Bajenoff, Marc, additional, Ng, Lai Guan, additional, Angeli, Veronique, additional, and Ginhoux, Florent, additional

Published
2019
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18. Neutrophils instruct homeostatic and pathological states in naive tissues

Author

Casanova-Acebes, Maria, primary, Nicolás-Ávila, José A., additional, Li, Jackson LiangYao, additional, García-Silva, Susana, additional, Balachander, Akhila, additional, Rubio-Ponce, Andrea, additional, Weiss, Linnea A., additional, Adrover, José M., additional, Burrows, Kyle, additional, A-González, Noelia, additional, Ballesteros, Ivan, additional, Devi, Sapna, additional, Quintana, Juan A., additional, Crainiciuc, Georgiana, additional, Leiva, Magdalena, additional, Gunzer, Matthias, additional, Weber, Christian, additional, Nagasawa, Takashi, additional, Soehnlein, Oliver, additional, Merad, Miriam, additional, Mortha, Arthur, additional, Ng, Lai Guan, additional, Peinado, Hector, additional, and Hidalgo, Andrés, additional

Published
2018
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19. Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis

Author

Mencarelli, Andrea, primary, Khameneh, Hanif Javanmard, additional, Fric, Jan, additional, Vacca, Maurizio, additional, El Daker, Sary, additional, Janela, Baptiste, additional, Tang, Jing Ping, additional, Nabti, Sabrina, additional, Balachander, Akhila, additional, Lim, Tong Seng, additional, Ginhoux, Florent, additional, Ricciardi-Castagnoli, Paola, additional, and Mortellaro, Alessandra, additional

Published
2018
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21. Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis.

Author

Mencarelli, Andrea, Khameneh, Hanif Javanmard, Fric, Jan, Vacca, Maurizio, Daker, Sary El, Janela, Baptiste, Jing Ping Tang, Nabti, Sabrina, Balachander, Akhila, Tong Seng Lim, Ginhoux, Florent, Ricciardi-Castagnoli, Paola, and Mortellaro, Alessandra

Subjects
INFLAMMATORY bowel diseases, HOMEOSTASIS, B cells, IMMUNOLOGICAL tolerance, CELL populations, CELLS
Abstract

The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chighMHCII+ cells (Cnb1CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin–NFAT–IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine. [ABSTRACT FROM AUTHOR]

Published
2018
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25. Tissue-Resident CD169+ Macrophages Form a Crucial Front Line against Plasmodium Infection.

Author

Gupta, Pravesh, Lai, Si Min, Sheng, Jianpeng, Tetlak, Piotr, Balachander, Akhila, Claser, Carla, Renia, Laurent, Karjalainen, Klaus, and Ruedl, Christiane

Abstract

Summary Tissue macrophages exhibit diverse functions, ranging from the maintenance of tissue homeostasis, including clearance of senescent erythrocytes and cell debris, to modulation of inflammation and immunity. Their contribution to the control of blood-stage malaria remains unclear. Here, we show that in the absence of tissue-resident CD169 + macrophages, Plasmodium berghei ANKA (PbA) infection results in significantly increased parasite sequestration, leading to vascular occlusion and leakage and augmented tissue deposition of the malarial pigment hemozoin. This leads to widespread tissue damage culminating in multiple organ inflammation. Thus, the capacity of CD169 + macrophages to contain the parasite burden and its sequestration into different tissues and to limit infection-induced inflammation is crucial to mitigating Plasmodium infection and pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2016
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26. Tissue-Resident CD169+Macrophages Form a Crucial Front Line against PlasmodiumInfection

Author

Gupta, Pravesh, Lai, Si Min, Sheng, Jianpeng, Tetlak, Piotr, Balachander, Akhila, Claser, Carla, Renia, Laurent, Karjalainen, Klaus, and Ruedl, Christiane

Abstract

Tissue macrophages exhibit diverse functions, ranging from the maintenance of tissue homeostasis, including clearance of senescent erythrocytes and cell debris, to modulation of inflammation and immunity. Their contribution to the control of blood-stage malaria remains unclear. Here, we show that in the absence of tissue-resident CD169+macrophages, Plasmodium bergheiANKA (PbA) infection results in significantly increased parasite sequestration, leading to vascular occlusion and leakage and augmented tissue deposition of the malarial pigment hemozoin. This leads to widespread tissue damage culminating in multiple organ inflammation. Thus, the capacity of CD169+macrophages to contain the parasite burden and its sequestration into different tissues and to limit infection-induced inflammation is crucial to mitigating Plasmodiuminfection and pathogenesis.

Published
2016
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27. Author Correction: Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury.

Author

Claser, Carla, Nguee, Samantha Yee Teng, Balachander, Akhila, Howland, Shanshan Wu, Becht, Etienne, Gunasegaran, Bavani, Hartimath, Siddesh V., Lee, Audrey W. Q., Ho, Jacqueline Theng Theng, Ong, Chee Bing, Newell, Evan W., Goggi, Julian, Ng, Lai Guan, and Renia, Laurent

Subjects
ENDOTHELIAL cells, LUNG injuries
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Published
2019
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28. Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe.

Author

Kim Pin Yeo, Hwee Ying Lim, Chung Hwee Thiam, Azhar, Syaza Hazwany, Tan, Caris, Ya Tang, Wei Qiang See, Xuan Han Koh, Ming Hao Zhao, Meow Ling Phua, Balachander, Akhila, Yingrou Tan, Sheau Yng Lim, Hui Shang Chew, Lai Guan Ng, and Angeli, Veronique

Subjects
*AORTA, *BLOOD cholesterol, *EZETIMIBE, *ATHEROSCLEROSIS, *INTERNAL carotid artery, *DRAINAGE
Abstract

The article presents a study which examined the effectiveness of promoting lymphatic drainage as treatment of atherosclerosis. In the study, the aortic lymphatic transport of macromolecules is adversely affected during atherosclerosis progression. The disruption in lymphatic flow promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and prevents ezetimibe-induced atherosclesoris regression.

Published
2020
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29. Calcineurin-mediated IL-2 production by CD11c high MHCII + myeloid cells is crucial for intestinal immune homeostasis.

Author

Mencarelli A, Khameneh HJ, Fric J, Vacca M, El Daker S, Janela B, Tang JP, Nabti S, Balachander A, Lim TS, Ginhoux F, Ricciardi-Castagnoli P, and Mortellaro A

Subjects
Animals, CD11c Antigen genetics, Calcineurin genetics, Colitis genetics, Female, Genes, MHC Class II, Homeostasis, Humans, Interleukin-2 genetics, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Th1 Cells immunology, Th17 Cells immunology, CD11c Antigen immunology, Calcineurin immunology, Colitis immunology, Interleukin-2 immunology, Intestines immunology, Myeloid Cells immunology
Abstract

The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11c high MHCII + cells (Cnb1 CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3 + regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11c high MHCII + cells to express IL-2. Deleting IL-2 in CD11c high MHCII + cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.

Published
2018
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