Homing imprinting and immunomodulation in the gut: role of dendritic cells and retinoids.
Lymphocyte migration is at the heart of chronic inflammatory ailments, including inflammatory bowel disease (IBD). Whereas naïve lymphocytes migrate to all secondary lymphoid organs, they are mostly excluded from nonlymphoid peripheral tissues. Upon activation, lymphocytes change their pattern of adhesion receptors and acquire the capacity to migrate to extralymphoid tissues. Antigen-experienced T cells are subdivided into different subsets based on their expression of homing receptors that favor their accumulation in specific tissues, such as the skin and the gut mucosa. B cells and antibody-secreting cells (ASC) also show tissue-tropism, which is somewhat correlated with the class of immunoglobulin that they produce. In fact, IgA-ASC are located in mucosal tissues, where they produce IgA, the main class of antibodies found in secretions. Although IgA-ASC are usually considered as a homogeneous pool of cells, those located in the small bowel have some unique migratory characteristics, suggesting that they are generated under different conditions as compared to IgA-ASC in other mucosal compartments. Foxp3(+) regulatory T cells (T(REG)) can also exhibit tissue-specific migratory potential and recent evidence suggests that T(REG) can be imprinted with gut-specific homing. Moreover, foxp3(+) T(REG) are enriched in the small bowel lamina propria, where they can be generated locally. The present review addresses our current understanding of how tissue-specific homing is acquired and modulated on T cells, B cells, and ASC, with a special emphasis on the intestinal mucosa. Harnessing these mechanisms could offer novel, effective, and more specific therapeutic strategies in IBD.
Mora
J Rodrigo
JR
Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA. j_rodrigo_mora@hms.harvard.edu
D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D018448:Models, Immunological; D009928:Organ Specificity; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D014212:Tretinoin / Q000276:immunology*
D016201:Receptors, Lymphocyte Homing; D014212:Tretinoin