STAT 3 but not STAT 4 is critical for γδT17 cell responses and skin inflammation
| Autor: | Rasmus Agerholm, Monica Torrellas Viñals, Vasileios Bekiaris, John Rizk |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
Biopsy medicine.medical_treatment Cell Dermatitis Inflammation Biochemistry Immunophenotyping Immunomodulation Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Psoriasis Lymphocyte Count STAT3 Molecular Biology STAT4 030304 developmental biology 0303 health sciences biology Lymphocyte differentiation Interleukin Receptors Antigen T-Cell gamma-delta STAT4 Transcription Factor Cell biology Disease Models Animal medicine.anatomical_structure Cytokine biology.protein Cytokines Th17 Cells Disease Susceptibility Inflammation Mediators medicine.symptom Biomarkers 030217 neurology & neurosurgery Homeostasis Reports |
| Zdroj: | EMBO Rep |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201948647 |
| Popis: | The transcription factors STAT3 and STAT4 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 STAT3 and STAT4 in regulating the homeostasis, activation, and pathogenicity of γδT17 cells. We show that STAT3 sustains γδT17 numbers in the skin but not in the lymph nodes, while STAT4 deficiency does not affect their homeostasis. Similarly, STAT3 but not STAT4 is essential for IL‐23‐induced IL‐22 production by γδT17 cells. Concomitantly, mice lacking STAT3 expression in γδT17 cells develop significantly reduced psoriasis‐like inflammation. STAT3‐deficient γδT17 cells fail to expand and to upregulate IL‐17A, IL‐17F, and IL‐22 in response to psoriatic stimuli. Although STAT4‐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 STAT3 in orchestrating the homeostasis and pathogenicity of γδT17 cells and provide evidence for the requirement of STAT4 for optimal cytokine responses during inflammation. |
| Databáze: | OpenAIRE |
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