期刊
FRONTIERS IN IMMUNOLOGY
卷 4, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2013.00155
关键词
tTreg; pTreg; IL-2; TNF-alpha; TGF-beta; regulatory T cells; Foxp3
类别
资金
- Ministere de l'Enseignement Superieur et de la Recherche
- Universite Pierre et Marie Curie, Paris 06
- EFSD/JDRF/NN
- INSERM/DGOS
- ANRS
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are essential players in the control of immune responses. Recently, accordingly to their origin, two main subsets of Tregs have been described: thymus-derived Tregs (tTregs) and peripherally derived Tregs (pTregs). Numerous signaling pathways including the IL-2/STAT5 or the TGF-beta/Smad3 pathways play a crucial role in segregating the two lineages. Here, we review some of the information existing on the distinct requirements of IL-2, TGF-beta, and TNF-alpha three major cytokines involved in tTreg and pTreg generation, homeostasis and function. Today it is clear that signaling via the IL-2R beta chain (CD122) common to IL-2 and IL-15 is required for proper differentiation of tTregs and for tTreg and pTreg survival in the periphery. This notion has led to the development of promising therapeutic strategies based on low-dose IL-2 administration to boost the patients' own Treg compartment and dampen autoimmunity and inflammation. Also, solid evidence points to TGF-beta as the master regulator of pTreg differentiation and homeostasis. However, therapeutic administration of TGF-beta is difficult to implement due to toxicity and safety issues. Knowledge on the role of TNF-alpha on the biology of Tregs is fragmentary and inconsistent between mice and humans. Moreover, emerging results from the clinical use of TNF-alpha inhibitors indicate that part of their anti-inflammatory effect may be dependent on their action on Tregs. Given the profusion of clinical trials testing cytokine administration or blocking to modulate inflammatory diseases, a better knowledge of the effects of cytokines on tTregs and pTregs biology is necessary to improve the efficiency of these immunotherapies.
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