scholarly journals Feline Glycoprotein A Repetitions Predominant Anchors Transforming Growth Factor Beta on the Surface of Activated CD4+CD25+Regulatory T Cells and Mediates AIDS Lentivirus-Induced T Cell Immunodeficiency

2013 ◽  
Vol 29 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Michelle M. Miller ◽  
Jonathan E. Fogle ◽  
Peter Ross ◽  
Mary B. Tompkins
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
T Cell Immunodeficiency ◽  
Growth Factor Beta

scholarly journals Smad7 in intestinal CD4+T cells determines autoimmunity in a spontaneous model of multiple sclerosis

2019 ◽  
Vol 116 (51) ◽  
pp. 25860-25869 ◽  
Author(s):  
Steffen Haupeltshofer ◽  
Teresa Leichsenring ◽  
Sarah Berg ◽  
Xiomara Pedreiturria ◽  
Stephanie C. Joachim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Intestinal Barrier ◽  
Cns Inflammation ◽  
Growth Factor Beta ◽  
And Migration

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.

Sign in / Sign up

Export Citation Format

Share Document