IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells

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RESEARCH PRODUCT

IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells

Francesco Pallone Christoph Becker Daniele Fina Roberta Caruso Agelamaria Rizzo Thomas T. Macdonald Markus F. Neurath Giovanni Monteleone Massimo Fantini

subject

Adoptive cell transfer medicine.medical_treatment Immunology Cell Gene Expression chemical and pharmacologic phenomena Mice SCID Biology T-Lymphocytes Regulatory Mice Immune system T-Lymphocyte Subsets Transforming Growth Factor beta FoxP3 IL-21 medicine Animals Immunology and Allergy RNA Messenger IL-2 receptor Transcription factor Settore MED/12 - Gastroenterologia Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Interleukins Interleukin-17 FOXP3 Forkhead Transcription Factors hemic and immune systems Colitis Flow Cytometry Adoptive Transfer Cell biology Colitis; FoxP3; IL-21; Treg cells; TGF-Î² TGF-Î² Disease Models Animal medicine.anatomical_structure Cytokine Immunology Treg cells Homeostasis

description

Regulatory T (T(reg)) cells play a key role in the maintenance of the immune system homeostasis. T(reg) cells can be generated in the periphery under control of TGF-beta, a cytokine involved in the negative control of the immune system. However, TGF-beta cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF-beta emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF-beta-dependent expression of FoxP3, the master regulator of T(reg) cell commitment, and the induction of suppressive capacity in naive CD4(+) T cells, while promoting the differentiation of Th17 cells. In vivo, CD4(+) naive T cells activated in the presence of TGF-beta and IL-21 failed to suppress colitis while inducing an inflammatory response characterized by high levels of IL-17 and RORgammat, the transcription factor expressed by Th17 cells. Therefore, IL-21 emerges as a key modulator of TGF-beta signaling, leading to the reciprocal differentiation of T(reg) and Th17 cells.

year	journal	country	edition	language
2007-10-06	European Journal of Immunology

https://doi.org/10.1002/eji.200737766