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Hammerschmidt, S.I.* ; Friedrichsen, M.* ; Boelter, J.* ; Lyszkiewicz, M.* ; Kremmer, E. ; Pabst, O.* ; Forster, R.*

Retinoic acid induces homing of protective T and B cells to the gut after subcutaneous immunization in mice.

J. Clin. Invest. 121, 3051-3061 (2011)
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Diarrheal diseases represent a major health burden in developing countries. Parenteral immunization typically does not induce efficient protection against enteropathogens because it does not stimulate migration of immune cells to the gut. Retinoic acid (RA) is critical for gut immunity, inducing upregulation of gut-homing receptors on activated T cells. In this study, we have demonstrated that RA can redirect immune responses elicited by s.c. vaccination of mice from skin-draining inguinal LNs (ingLNs) to the gut. When present during priming, RA induced robust upregulation of gut-homing receptors in ingLNs, imprinting gut-homing capacity on T cells. Concurrently, RA triggered the generation of gut-tropic IgA+ plasma cells in ingLNs and raised the levels of antigen-specific IgA in the intestinal lumen and blood. RA applied s.c. in vivo induced autonomous RA production in ingLN DCs, further driving efficient induction of gut-homing molecules on effector cells. Importantly, RA-supplemented s.c. immunization elicited a potent immune response in the small intestine that protected mice from cholera toxin-induced diarrhea and diminished bacterial loads in Peyer patches after oral infection with Salmonella. Thus, the use of RA as a gut-homing navigator represents a powerful tool to induce protective immunity in the intestine after s.c. immunization, offering what we believe to be a novel approach for vaccination against enteropathogens.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter DENDRITIC CELLS; VITAMIN-A; RESPONSE ELEMENT; SMALL-INTESTINE; MUCOSAL; GENERATION; RECEPTOR; SKIN; CONTRIBUTES; GENE
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Zeitschrift Journal of Clinical Investigation
Quellenangaben Band: 121, Heft: 8, Seiten: 3051-3061 Artikelnummer: , Supplement: ,
Verlag American Society of Clinical Investigation
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)