Contextual regulation of inflammation:: A duet by transforming growth factor-β and interleukin-10
被引:501
作者:
Li, Ming O.
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机构:
Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USAMem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA
Li, Ming O.
[1
]
Flavell, Richard A.
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机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USAMem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA
Flavell, Richard A.
[2
,3
]
机构:
[1] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA
[2] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
Transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) are regulatory cytokines with pleiotropic roles in the immune system. The prominent function of TGF-beta is to maintain T cell tolerance to self or innocuous environmental antigens via its direct effects on the differentiation and homeostasis of effector and regulatory T cells. A critical route for the regulation of T cells by TGF-beta is via activation of a T cell-produced latent form of TGF-beta 1 by dendritic cell-expressed av beta 8 integrin. IL-10 operates primarily as a feedback inhibitor of exuberant T cell responses to microbial antigens. T cells are also the principal producers of IL-10, the expression of which is regulated by IL-27, IL-6, and TGF-beta. The collective activity of TGF-beta and IL-10 ensures a controlled inflammatory response specifically targeting pathogens without evoking excessive immunopathology to self-tissues.