CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.
Distinct classes of protective immunity are guided by activation of STAT transcription factor family members in response to environmental cues. CD4+ regulatory T cells (T(regs)) suppress excessive immune responses, and their deficiency results in a lethal, multi-organ autoimmune syndrome characterized by T helper 1 (TH1) and T helper 2 (TH2) CD4+ T cell-dominated lesions. Here we show that pathogenic TH17 responses in mice are also restrained by T(regs). This suppression was lost upon T(reg)-specific ablation of Stat3, a transcription factor critical for TH17 differentiation, and resulted in the development of a fatal intestinal inflammation. These findings suggest that T(regs) adapt to their environment by engaging distinct effector response-specific suppression modalities upon activation of STAT proteins that direct the corresponding class of the immune response.
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Ashutosh
A
Chaudhry
Dipayan
D
Rudra
Piper
P
Treuting
Robert M
RM
Samstein
Yuqiong
Y
Liang
Arnold
A
Kas
Alexander Y
AY
Rudensky
D000818:Animals; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007420:Intestine, Large / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C498126:CCR6 protein, mouse; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D054399:Receptors, CCR6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D007371:Interferon-gamma