Editors' ChoiceImmunology

Keeping the Peace: Skin Sentinels Maintain Immune Tolerance

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Science Translational Medicine  23 May 2012:
Vol. 4, Issue 135, pp. 135ec88
DOI: 10.1126/scitranslmed.3004310

Being “thick-skinned” may now apply to more than emotional reactivity. Immune regulation in peripheral tissues, such as the skin, is essential to maintaining tissue homeostasis. Dendritic cells (DCs) have been implicated in immune regulation in the skin of mice; however, their role in humans is less well defined. Chu et al. build on prior work to demonstrate that human skin contains specialized DCs that keep the peace by maintaining tolerance to self-antigens and reduce transplant rejection.

DCs are specialized immune cells that present antigens to T cells; they have the unique ability to translate microbial triggers, such as double-stranded RNA present in viruses, into T cell activating signals. When licensed by innate triggers, DCs can initiate T cell responses that result in the development of immune effector T cells and long-term memory. However, in some conditions DCs also maintain immune tolerance to self and contribute to tissue homeostasis. Chu et al. examine this latter function by isolating DCs directly from human skin. The authors observe that CD141+ DCs, but not another type of skin-resident DC, can process and present a model self-antigen, suggesting that these cells could be important in preventing autoreactivity to dead or dying cells. Indeed, CD141+ DC produced interleukin-10 and induced CTLA4high CD25+ regulatory T cells. In contrast to CD25+ cells induced by another skin DC subset, CD141+-induced CD25+ T cells were able to suppress other effector T cells from expanding, prevent graft rejection in a model of graft-versus-host disease, and inhibited tumor alloimmunity to melanoma. Cells with similar function from the blood could be induced with vitamin D3, suggesting that these cells may be useful in a clinical transplant setting or could trigger vitamin D–mediated immune suppression. Indeed, this connection with vitamin D suggests that ultraviolet-induced vitamin D signaling may influence a variety of inflammatory skin diseases by invoking these tolerance-inducing cells.

C.-C. Chu et al., Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J. Exp. Med. 209, 935–945 (2012). [Abstract]

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