التفاصيل البيبلوغرافية
| العنوان: |
TNF plays a crucial role in inflammation by signaling via T cell TNFR2. |
| المؤلفون: |
Alam, Muhammad S., Shizuka Otsuka, Wong, Nathan, Abbasi, Aamna, Gaida, Matthias M., Yu Fan, Meerzaman, Daoud, Ashwell, Jonathan D. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 12/14/2021, Vol. 118 Issue 50, p1-9, 9p |
| مصطلحات موضوعية: |
T cells, T helper cells, GRANULOCYTE-macrophage colony-stimulating factor, TH1 cells, TUMOR necrosis factor receptors, COMMERCIAL products |
| مستخلص: |
TNF, produced largely by T and innate immune cells, is potently proinflammatory, as are cytokines such as IFN-γ and IL-17 produced by Th1 and Th17 cells, respectively. Here, we asked if TNF is upstream of Th skewing toward inflammatory phenotypes. Exposure of mouse CD4+ T cells to TNF and TGF-β generated Th17 cells that express low levels of IL-17 (ROR-γt +IL-17lo) and high levels of inflammatory markers independently of IL-6 and STAT3. This was mediated by the nondeath TNF receptor TNFR2, which also contributed to the generation of inflammatory Th1 cells. Single-cell RNA sequencing of central nervous system–infiltrating CD4+ T cells in mouse experimental autoimmune encephalomyelitis (EAE) found an inflammatory gene expression profile similar to cerebrospinal fluid–infiltrating CD4+ T cells from patients with multiple sclerosis. Notably, TNFR2-deficient CD4+ T cells produced fewer inflammatory mediators and were less pathogenic in EAE and colitis. IL-1β, a Th17-skewing cytokine, induced TNF and proinflammatory granulocyte-macrophage colony-stimulating factor (GM-CSF) in T cells, which was inhibited by disruption of TNFR2 signaling, demonstrating IL-1β can function indirectly via the production of TNF. Thus, TNF is not just an effector but also an initiator of inflammatory Th differentiation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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