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13 results on '"Khoyratty, Tariq"'

2. Interferon regulatory factor 5 : a systematic study of macrophage gene regulation

Author

Khoyratty, Tariq, Udalova, Irina, and Proudfoot, Nicholas J.

Subjects
616.07, Immunology, Macrophage, Transcription, IRF5
Abstract

Macrophages are multifaceted innate immune cells, able to adapt their phenotype to respond to a myriad of conditions, engaging in tissue-specific functions and mediating either inflammatory or anti-inflammatory responses depending on the encountered stimuli. They conduct key roles in the orchestration of immune responses; from pathogen recognition through sterilising inflammation to resolution and repair. The Udalova laboratory has previously demonstrated that IRF5 promotes a pro- inflammatory macrophage phenotype, leading to the secretion of TNF, IL-12, and IL-23, enhancing Th1/Th17-mediated immune responses, and described the cooperation between IRF5 and the transcription factor RelA, which mediate the production of pro-inflammatory genes. The aim of this thesis is to further characterise the activity of IRF5 in macrophage inflammatory responses. I demonstrate that IRF5 not only regulates the transcription of cytokines and chemokines in response to bacterial stimuli, but also anti-microbial peptides, whilst simultaneously down-regulating homeostatic and resolving macrophage functions. My data also suggests that IRF5 plays a role in enforcing monocyte to macrophage differentiation by up-regulating the transcription of key macrophages markers and repressing dendritic cell identity genes. To further characterise the mechanisms of the inflammatory response mounted by macrophages I used an unbiased approach; combining twenty-three transcription factor ChIP-seq data sets with chromatin accessibility information from ATAC-seq, uncovering RUNX1 as a novel partner of IRF5 that binds co-operatively to clusters of enhancers, which control the transcription of pro-inflammatory genes in a signal-dependent manner. This is the first study demonstrating a critical role for RUNX1 in activity of inflammatory macrophages.

Published
2017

5. Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis

Author

Edgar, Laurienne, primary, Akbar, Naveed, additional, Braithwaite, Adam T., additional, Krausgruber, Thomas, additional, Gallart-Ayala, Héctor, additional, Bailey, Jade, additional, Corbin, Alastair L., additional, Khoyratty, Tariq E., additional, Chai, Joshua T., additional, Alkhalil, Mohammad, additional, Rendeiro, André F., additional, Ziberna, Klemen, additional, Arya, Ritu, additional, Cahill, Thomas J., additional, Bock, Christoph, additional, Laurencikiene, Jurga, additional, Crabtree, Mark J., additional, Lemieux, Madeleine E., additional, Riksen, Niels P., additional, Netea, Mihai G., additional, Wheelock, Craig E., additional, Channon, Keith M., additional, Rydén, Mikael, additional, Udalova, Irina A., additional, Carnicer, Ricardo, additional, and Choudhury, Robin P., additional

Published
2021
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6. The Zinc Finger Protein Zbtb18 Represses Expression of Class I Phosphatidylinositol 3-Kinase Subunits and Inhibits Plasma Cell Differentiation

Author

Xie, Bin, primary, Khoyratty, Tariq E., additional, Abu-Shah, Enas, additional, F. Cespedes, Pablo, additional, MacLean, Andrew J., additional, Pirgova, Gabriela, additional, Hu, Zhiyuan, additional, Ahmed, Ahmed A., additional, Dustin, Michael L., additional, Udalova, Irina A., additional, and Arnon, Tal I., additional

Published
2021
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7. Co-option of Neutrophil Fates by Tissue Environments

Author

Ballesteros, Iván, primary, Rubio-Ponce, Andrea, additional, Genua, Marco, additional, Lusito, Eleonora, additional, Kwok, Immanuel, additional, Fernández-Calvo, Gabriel, additional, Khoyratty, Tariq E., additional, van Grinsven, Erinke, additional, González-Hernández, Sara, additional, Nicolás-Ávila, José Ángel, additional, Vicanolo, Tommaso, additional, Maccataio, Antonio, additional, Benguría, Alberto, additional, Li, Jackson LiangYao, additional, Adrover, José M., additional, Aroca-Crevillen, Alejandra, additional, Quintana, Juan A., additional, Martín-Salamanca, Sandra, additional, Mayo, Francisco, additional, Ascher, Stefanie, additional, Barbiera, Giulia, additional, Soehnlein, Oliver, additional, Gunzer, Matthias, additional, Ginhoux, Florent, additional, Sánchez-Cabo, Fátima, additional, Nistal-Villán, Estanislao, additional, Schulz, Christian, additional, Dopazo, Ana, additional, Reinhardt, Christoph, additional, Udalova, Irina A., additional, Ng, Lai Guan, additional, Ostuni, Renato, additional, and Hidalgo, Andrés, additional

Published
2020
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8. ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies

Author

Wang, Lihui, primary, Ai, Zhichao, additional, Khoyratty, Tariq, additional, Zec, Kristina, additional, Eames, Hayley L., additional, van Grinsven, Erinke, additional, Hudak, Alison, additional, Morris, Susan, additional, Ahern, David, additional, Monaco, Claudia, additional, Eruslanov, Evgeniy B., additional, Luqmani, Raashid, additional, and Udalova, Irina A., additional

Published
2020
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9. PYK2 controls intestinal inflammation via activation of IRF5 in macrophages

Author

Ryzhakov, Grigory, primary, Almuttaqi, Hannah, additional, Corbin, Alastair L., additional, Khoyratty, Tariq, additional, Berthold, Dorothee, additional, Bullers, Samuel, additional, Eames, Hayley L, additional, Ai, Zhichao, additional, Bonham, Sarah, additional, Fischer, Roman, additional, Jostins-Dean, Luke, additional, Travis, Simon P.L., additional, Kessler, Benedikt M., additional, and Udalova, Irina A., additional

Published
2020
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10. Antibody response to homologous epitopes of Epstein-Barr virus, Mycobacterium avium subsp. paratuberculosis and IRF5 in patients with different connective tissue diseases and in mouse model of antigen-induced arthritis

Author

Bo, Marco, primary, Niegowska, Magdalena, additional, Eames, Hayley L., additional, Almuttaqi, Hannah, additional, Arru, Giannina, additional, Erre, Gian Luca, additional, Passiu, Giuseppe, additional, Khoyratty, Tariq E., additional, van Grinsven, Erinke, additional, Udalova, Irina A., additional, and Sechi, Leonardo A., additional

Published
2020
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11. The Zinc Finger Protein Zbtb18 Represses Expression of Class I Phosphatidylinositol 3-Kinase Subunits and Inhibits Plasma Cell Differentiation.

Author

Bin Xie, Khoyratty, Tariq E., Abu-Shah, Enas, Cespedes, Pablo F., MacLean, Andrew J., Pirgova, Gabriela, Zhiyuan Hu, Ahmed, Ahmed A., Dustin, Michael L., Udalova, Irina A., and Arnon, Tal I.

Subjects
*ZINC-finger proteins, *PLASMA cells, *CELL differentiation, *B cells, *PROMOTERS (Genetics)
Abstract

The PI3K pathway plays a key role in B cell activation and is important for the differentiation of Ab producing plasma cells (PCs). Although much is known about the molecular mechanisms that modulate PI3K signaling in B cells, the transcriptional regulation of PI3K expression is poorly understood. In this study, we identify the zinc finger protein Zbtb18 as a transcriptional repressor that directly binds enhancer/promoter regions of genes encoding class I PI3K regulatory subunits, subsequently limiting their expression, dampening PI3K signaling and suppressing PC responses. Following activation, dividing B cells progressively downregulated Zbtb18, allowing gradual amplification of PI3K signals and enhanced development of PCs. Human Zbtb18 displayed similar expression patterns and function in human B cells, acting to inhibit development of PCs. Furthermore, a number of Zbtb18 mutants identified in cancer patients showed loss of suppressor activity, which was also accompanied by impaired regulation of PI3K genes. Taken together, our study identifies Zbtb18 as a repressor of PC differentiation and reveals its previously unappreciated function as a transcription modulator of the PI3K signaling pathway. [ABSTRACT FROM AUTHOR]

Published
2021
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