Author: Tsuji, Noriko M.

Source: Inflammation & Allergy - Drug Targets, Volume 5, Number 3, September 2006 , pp. 191-201(11)

Publisher: Bentham Science Publishers

Abstract:

Mucosal surfaces, especially the gastrointestinal (GI) tract, are obligatory sites for tolerance induction against numerous exogenous antigens. Therefore, the mucosal surface seems to provide a microenvironment conductive to the induction of antigen-specific regulatory T cells. The cytokine milieu, which includes IL-10 and TGF-β , affects effector function of local dendritic cells and induces regulatory T cells (iTREG). During immune homeostasis (steady state) in the GI tract, noninflammatory innate immune signals provided by innocuous or commensal bacteria seem to play important roles in the induction of regulatory cytokines that enable the establishment of tolerance, which involves iTREG function. In accordance with this viewpoint, utilizing physiological means such as probiotics and TLR ligands may improve the homeostatic conditions of immune-mediated diseases and inflammation. Antigen-specific iTREG is a great counterpart of thymus-derived CD25+CD4+Foxp3+ TREG (nTREG), and therefore clinical applications of TREG should be developed that integrate the advantages of both of these cell populations. Close investigation of mucosal iTREG and related microenvironments not only will facilitate novel interventions of mucosal immunity but also will help to best utilize iTREG and iTREG in an integrated way.

Keywords: Regulatory T cells; Antigen; Oral tolerance; Mucosal immunity; Regulatory dendritic cells; L-10; TGF-β; probiotics

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152806778256043

Affiliations: 1: AIST Tsukuba Central 6-13,1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.

Publication date: 2006-09-01

More about this publication?

• Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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