Harnessing DCs by substance P.

摘要

Nerve fibers project to virtually all organs of the body not only to monitor the external environment, but also to control the internal homeostasis. Neutropeptides released from nerve fibers (and inflammatory leukocytes) facilitate the immune system to accomplish its 2 opposing tasks of maintaining immune tolerance to self-antigens, while inducing robust immune responses against external insults. A wide variety of neutropeptides have been shown to suppress host inflammatory and immune responses. These anti-inflammatory neutropeptides include vasoactive intestinal peptide (VIP), a-melanocyte-stimulating hormone (a-MSH), calcitonin gene-related peptide (CGRP), adrenomedullin, urocortin, and cortistatin.2 VIP and a-MSH are both known to inhibit phagocytic activities of innate leukocytes, such as neutrophils and macrophages. Moreover, VIP and a-MSH maintain T helper 2 (Th2)-biased immune balance by acting directly on differentiating T cells, as well as on DCs (see figure). VIP, a-MSH, and CGRP have been shown to downregulate surface expression of costimulatory molecules and production of inflammatory cytokines (eg, IL-1, IL-6, and tumor necrosis factor a [TNFa]) and IL-12 by DCs, while augmenting their production of IL-10.2"4 The resulting "tolerogenic" DCs, in turn, induce immunologic tolerance by favoring Th2-biased immunity and promoting the generation of regulatory T cells.2'3