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Mucosal Immunol. 2008 Mar;1(2):92-5. doi: 10.1038/mi.2007.22. Epub 2008 Jan 16.

Vitamin A rewrites the ABCs of oral tolerance.

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  • 1Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.


One of the chief requirements of an immune system, the mucosal immune system, that lies juxtaposed to a mass of potentially immunogenic commensal organisms is a well-developed mechanism to limit or negatively regulate nascent immune responses to those organisms. This mechanism, long subsumed under the name oral tolerance, is now understood to consist of a complex of factors, not the least of which is the ready ability to induce immunosuppressive regulatory T cells or Tregs. The emphasis here is on the "ability to induce" because the real individuality of the mucosal regulatory response lies not in the Tregs themselves, which after all can be induced anywhere and are mere tools of regulatory response. Now, as shown initially by the fact that oral tolerance is dependent on the size and mobility of its dendritic cell (DC) population, the individuality of the mucosal immune system is inherent in its inducing cells, i.e., the antigen-presenting DCs (or macrophages) of the mucosal immune system.(1, 2)Recently, new data have emerged that provide much more specific information on how mucosal DCs (or macrophages) are different in this respect and thus why they have a special tendency to facilitate the development of Tregs that then mediate oral tolerance. This is the subject of this brief review. The unresponsiveness of mucosal immune system to mucosal antigens is due to a process known as oral tolerance. Recent studies addressing the mechanism of such tolerance show that mucosal tissues are replete with a unique subset of dendritic cells that secrete factors such as, TGF-beta1 and retinoic acid, that induce foxp3+ regulatory T cells. Thus, we arrive at the somewhat surprising realization that mucosal unresponsiveness is, appropriately enough, related to the availability of a factor in the food stream.

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