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STAT 3 but not STAT 4 is critical for γδT17 cell responses and skin inflammation
Author(s) -
Agerholm Rasmus,
Rizk John,
Viñals Mònica Torrellas,
Bekiaris Vasileios
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948647
Subject(s) - stat4 , stat3 , interleukin 17 , immunology , stat , inflammation , interleukin 23 , biology , cytokine , interleukin , microbiology and biotechnology , signal transduction
The transcription factors STAT 3 and STAT 4 are essential for lymphocyte differentiation and function. Interleukin ( IL )‐17 producing γδ T (γδT17) cells are innate lymphocytes important for anti‐bacterial and inflammatory responses at barrier surfaces. Herein, we examine the role of STAT 3 and STAT 4 in regulating the homeostasis, activation, and pathogenicity of γδT17 cells. We show that STAT 3 sustains γδT17 numbers in the skin but not in the lymph nodes, while STAT 4 deficiency does not affect their homeostasis. Similarly, STAT 3 but not STAT 4 is essential for IL ‐23‐induced IL ‐22 production by γδT17 cells. Concomitantly, mice lacking STAT 3 expression in γδT17 cells develop significantly reduced psoriasis‐like inflammation. STAT 3‐deficient γδT17 cells fail to expand and to upregulate IL ‐17A, IL ‐17F, and IL ‐22 in response to psoriatic stimuli. Although STAT 4‐deficient animals develop psoriasis‐like disease, γδT17 cells in these mice are defective in IL ‐17F production. Collectively, our data demonstrate for the first time a critical role for STAT 3 in orchestrating the homeostasis and pathogenicity of γδT17 cells and provide evidence for the requirement of STAT 4 for optimal cytokine responses during inflammation.