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1.
Nat Immunol ; 24(12): 2108-2120, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932457

RESUMO

Regulatory T cells (Treg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Treg cells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a new Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.


Assuntos
Interleucina-27 , Linfócitos T Reguladores , Camundongos , Animais , Linfócitos T Auxiliares-Indutores , Tolerância Imunológica , Imunidade Celular , Células Th17
2.
J Exp Med ; 220(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37516921

RESUMO

Effector regulatory T cells (eTregs) exhibit distinct homeostatic properties and superior suppressor capacities pivotal for controlling immune responses mediated by their conventional T cell counterpart. While the role of microRNAs (miRNAs) in Tregs has been well-established, how miRNAs regulate eTregs remains poorly understood. Here, we demonstrate that miR-15/16 clusters act as key regulators in limiting eTreg responses. Loss of miR-15/16 clusters leads to increased eTreg frequencies with enhanced suppressor function. Consequently, mice with Treg-specific ablation of miR-15/16 clusters display attenuated immune responses during neuroinflammation and upon both infectious and non-infectious challenges. Mechanistically, miR-15/16 clusters exert their regulatory effect in part through repressing IRF4, a transcription factor essential for eTreg differentiation and function. Moreover, miR-15/16 clusters also directly target neuritin, an IRF4-dependent molecule, known for its role in Treg-mediated regulation of plasma cell responses. Together, we identify an miRNA family that controls an important Treg subset and further demonstrate that eTreg responses are tightly regulated at both transcriptional and posttranscriptional levels.


Assuntos
MicroRNAs , Linfócitos T Reguladores , Animais , Camundongos , Ativação Linfocitária , Diferenciação Celular/genética , Homeostase , MicroRNAs/genética
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