Avaliações PREreview de “Serum Amyloid A Proteins Induce Pathogenic TH17 Cells and Promote Inflammatory Disease”

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Serum Amyloid A Proteins Induce Pathogenic T_H17 Cells and Promote Inflammatory Disease

de June-Yong Lee, Jason A. Hall, Lina Kroehling, Lin Wu, Tariq Najar, Henry H. Nguyen, Woan-Yu Lin, Stephen T. Yeung, Hernandez Moura Silva, Dayi Li, Ashley Hine, P’ng Loke, David Hudesman, Jerome C. Martin, Ephraim Kenigsberg, Miriam Merad, Kamal M. Khanna e Dan R. Littman

Publicado: 25 de junho de 2019
Servidor: bioRxiv
DOI: 10.1101/681346

Resumo

Summary

Lymphoid cells that produce IL-17 cytokines protect barrier tissues from pathogenic microbes, but are also prominent effectors of inflammation and autoimmune disease. T-helper (T_H17) cells, defined by RORγt-dependent production of IL-17A and IL-17F, exert homeostatic functions in the gut upon microbiota-directed differentiation from naïve CD4⁺ T cells. In the non-pathogenic setting, their cytokine production is regulated by serum amyloid A proteins (SAA1 and SAA2) secreted by adjacent intestinal epithelial cells. However, T_H17 cell behaviors vary markedly according to their environment. Here we show that SAAs additionally direct a pathogenic pro-inflammatory T_H17 cell differentiation program, acting directly on T cells in collaboration with STAT3-activating cytokines. Using loss- and gain-of-function mouse models, we show that SAA1, SAA2, and SAA3 have distinct systemic and local functions in promoting T_H17-mediated inflammatory diseases. These studies suggest that T cell signaling pathways modulated by the SAAs may be attractive targets for anti-inflammatory therapies.

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Avaliações PREreview de Serum Amyloid A Proteins Induce Pathogenic TH17 Cells and Promote Inflammatory Disease

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Avaliações PREreview de Serum Amyloid A Proteins Induce Pathogenic T_H17 Cells and Promote Inflammatory Disease