Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine

Yukiko K. Nakamura, Cathleen Janowitz, Christina Metea, Mark Asquith, Lisa Karstens, James (Jim) Rosenbaum, Phoebe Lin

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19 Citations (Scopus)

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.

Original languageEnglish (US)
Article number11745
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Volatile Fatty Acids
Uveitis
Intestines
Lymphocytes
Lymph Nodes
Propionates
Leukocytes
Animal Disease Models
Dietary Fiber
Regulatory T-Lymphocytes
Transgenic Mice
Fermentation
Cell Movement
Gastrointestinal Tract
Mucous Membrane
Theoretical Models
Spleen
Bacteria
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • General

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Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine. / Nakamura, Yukiko K.; Janowitz, Cathleen; Metea, Christina; Asquith, Mark; Karstens, Lisa; Rosenbaum, James (Jim); Lin, Phoebe.

In: Scientific Reports, Vol. 7, No. 1, 11745, 01.12.2017.

Research output: Contribution to journalArticle

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