TY  - JOUR
AU  - Haupeltshofer, Steffen
AU  - Leichsenring, Teresa
AU  - Berg, Sarah
AU  - Pedreiturria, Xiomara
AU  - Joachim, Stephanie C.
AU  - Tischoff, Iris
AU  - Otte, Jan-Michel
AU  - Bopp, Tobias
AU  - Fantini, Massimo C.
AU  - Esser, Charlotte
AU  - Willbold, Dieter
AU  - Gold, Ralf
AU  - Faissner, Simon
AU  - Kleiter, Ingo
TI  - Smad7 in intestinal CD4 + T cells determines autoimmunity in a spontaneous model of multiple sclerosis
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 116
IS  - 51
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - FZJ-2020-00226
SP  - 25860 - 25869
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31796589
UR  - <Go to ISI:>//WOS:000503281500070
DO  - DOI:10.1073/pnas.1905955116
UR  - https://juser.fz-juelich.de/record/872748
ER  -