Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells.
Antibody-secreting cells (ASCs) lodging in the mucosa of the small intestine are derived from activated B cells that are thought to arise in gut-associated lymphoid tissues (GALT). Upon leaving the GALT, B cells return to the blood where they must express the gut-homing receptors alpha4beta7 and CCR9 in order to emigrate into the small bowel. Recent evidence indicates that gut-associated dendritic cells (DCs) in GALT induce gut-homing receptors on B cells via a mechanism that depends on the vitamin A metabolite retinoic acid (RA). In addition, although ASC associated with other mucosal tissues secrete IgA in an RA-independent fashion, the presence of high levels of RA in intestine and GALT can promote B cell class switching to IgA and thus, boost the production of IgA in the intestinal mucosa. Here, we discuss the role of RA in the imprinting of gut-homing ASC and the evidence linking RA with the generation of intestinal IgA-ASCs.
Mora
J Rodrigo
JR
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ-815, Boston, MA 02114, USA. j_rodrigo_mora@hms.harvard.edu
von Andrian
Ulrich H
UH
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D054388:Receptors, CCR / Q000276:immunology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; D016207:Cytokines; D007070:Immunoglobulin A; D054388:Receptors, CCR; D011978:Receptors, Nicotinic; D014212:Tretinoin