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000872748 1001_ $$0P:(DE-HGF)0$$aHaupeltshofer, Steffen$$b0
000872748 245__ $$aSmad7 in intestinal CD4 + T cells determines autoimmunity in a spontaneous model of multiple sclerosis
000872748 260__ $$aWashington, DC$$bNational Acad. of Sciences$$c2019
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000872748 520__ $$aEnvironmental 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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000872748 7001_ $$0P:(DE-HGF)0$$aLeichsenring, Teresa$$b1
000872748 7001_ $$0P:(DE-HGF)0$$aBerg, Sarah$$b2
000872748 7001_ $$0P:(DE-HGF)0$$aPedreiturria, Xiomara$$b3
000872748 7001_ $$0P:(DE-HGF)0$$aJoachim, Stephanie C.$$b4
000872748 7001_ $$0P:(DE-HGF)0$$aTischoff, Iris$$b5
000872748 7001_ $$0P:(DE-HGF)0$$aOtte, Jan-Michel$$b6
000872748 7001_ $$0P:(DE-HGF)0$$aBopp, Tobias$$b7
000872748 7001_ $$0P:(DE-HGF)0$$aFantini, Massimo C.$$b8
000872748 7001_ $$0P:(DE-HGF)0$$aEsser, Charlotte$$b9
000872748 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b10$$ufzj
000872748 7001_ $$0P:(DE-HGF)0$$aGold, Ralf$$b11
000872748 7001_ $$0P:(DE-HGF)0$$aFaissner, Simon$$b12
000872748 7001_ $$00000-0002-8249-4408$$aKleiter, Ingo$$b13$$eCorresponding author
000872748 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.1905955116$$gVol. 116, no. 51, p. 25860 - 25869$$n51$$p25860 - 25869$$tProceedings of the National Academy of Sciences of the United States of America$$v116$$x1091-6490$$y2019
000872748 8564_ $$uhttps://juser.fz-juelich.de/record/872748/files/Smad7%20in%20intestinal%20CD4%2B%20T%20cells%20determines%20autoimmunity%20in%20a%20spontaneous%20model%20of%20multiple%20sclerosis.pdf$$yPublished on 2019-12-03. Available in OpenAccess from 2020-06-03.
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