Journal Article

FZJ-2020-00226

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Smad7 in intestinal CD4 + T cells determines autoimmunity in a spontaneous model of multiple sclerosis

Haupeltshofer, S. ; Leichsenring, T. ; Berg, S. ; Pedreiturria, X. ; Joachim, S. C. ; Tischoff, I. ; Otte, J.-M. ; Bopp, T. ; Fantini, M. C. ; Esser, C. ; Willbold, D.FZJ* ; Gold, R. ; Faissner, S. ; Kleiter, I. (Corresponding author)

2019
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/23873  doi:10.1073/pnas.1905955116

Abstract: Environmental triggers acting at the intestinal barrier are thought to contribute to the initiation of autoimmune disorders. The transforming growth factor beta inhibitor Smad7 determines the phenotype of CD4+ T cells. We hypothesized that Smad7 in intestinal CD4+ T cells controls initiation of opticospinal encephalomyelitis (OSE), a murine model of multiple sclerosis (MS), depending on the presence of gut microbiota. Smad7 was overexpressed or deleted in OSE CD4+ T cells to determine the effect on clinical progression, T cell differentiation, and T cell migration from the intestine to the central nervous system (CNS). Smad7 overexpression worsened the clinical course of OSE and increased CNS inflammation and demyelination. It favored expansion of intestinal CD4+ T cells toward an inflammatory phenotype and migration of intestinal CD4+ T cells to the CNS. Intestinal biopsies from MS patients revealed decreased transforming growth factor beta signaling with a shift toward inflammatory T cell subtypes. Smad7 in intestinal T cells might represent a valuable therapeutic target for MS to achieve immunologic tolerance in the intestine and suppress CNS inflammation.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2019

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; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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