RRC ID 49601
Author Nakamura YK, Janowitz C, Metea C, Asquith M, Karstens L, Rosenbaum JT, Lin P.
Title Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine.
Journal Sci Rep
Abstract Short chain fatty acids (SCFA) are metabolites of intestinal bacteria resulting from fermentation of dietary fiber. SCFA are protective in various animal models of inflammatory disease. We investigated the effects of exogenous administration of SFCAs, particularly propionate, on uveitis using an inducible model of experimental autoimmune uveitis (EAU). Oral SCFA administration attenuated uveitis severity in a mouse strain-dependent manner through regulatory T cell induction among lymphocytes in the intestinal lamina propria (LPL) and cervical lymph nodes (CLN). SCFA also suppressed effector T cell induction in the CLN and mesenteric lymph nodes (MLN). Alterations in intestinal morphology and gene expression demonstrated in the EAU model prior to the onset of uveitis were blunted by oral SCFA administration. Using a Kaede transgenic mouse, we demonstrated enhanced leukocyte trafficking between the intestine and the eye in EAU. Propionate suppressed T effector cell migration between the intestine and the spleen in EAU Kaede mice. In conclusion, our findings support exogenous administration of SCFAs as a potential treatment strategy for uveitis through the stabilization of subclinical intestinal alterations that occur in inflammatory diseases including uveitis, as well as prevention of trafficking of leukocytes between the gastrointestinal tract and extra-intestinal tissues.
Volume 7(1)
Pages 11745
Published 2017-9-18
DOI 10.1038/s41598-017-12163-3
PII 10.1038/s41598-017-12163-3
PMID 28924192
PMC PMC5603543
MeSH Animals Autoimmune Diseases / drug therapy* Autoimmune Diseases / immunology Autoimmune Diseases / pathology Cell Movement / drug effects* Cell Movement / immunology Disease Models, Animal Fatty Acids, Volatile / pharmacology* Female Intestines* / immunology Intestines* / pathology Mice T-Lymphocytes, Regulatory* / immunology T-Lymphocytes, Regulatory* / pathology Uveitis* / drug therapy Uveitis* / immunology Uveitis* / pathology
IF 3.998
Times Cited 25
Mice RBRC05737