Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018133 (
graft-versus-host disease
)
18,032
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Systemic sclerosis (SSc) is a debilitating inflammatory and fibrotic disease that affects the skin and internal organs. Although the pathophysiology of SSc remains poorly characterized, mononuclear cells, mainly macrophages and T cells, have been implicated in inflammation and fibrosis. Inducible costimulator (ICOS), which is expressed on a subset of memory T helper (T
H
) and T follicular helper (T
FH
) cells, has been shown to be increased in SSc and associated with disease pathology. However, the identity of the relevant ICOS
+
T cells and their contribution to inflammation and fibrosis in SSc are still unknown. We show that CD4
+
ICOS-expressing T cells with a T
FH
-like phenotype infiltrate the skin of patients with SSc and are correlated with dermal fibrosis and clinical disease status. ICOS
+
T
FH
-like cells were found to be increased in the skin of
graft-versus-host disease
(
GVHD
)-SSc mice and contributed to dermal fibrosis via an interleukin-21- and
matrix metalloproteinase 12
-dependent mechanism. Administration of an anti-ICOS antibody to
GVHD
-SSc mice prevented the expansion of ICOS
+
T
FH
-like cells and inhibited inflammation and dermal fibrosis. Interleukin-21 neutralization in
GVHD
-SSc mice blocked disease pathogenesis by reducing skin fibrosis. These results identify ICOS
+
T
FH
-like profibrotic cells as key drivers of fibrosis in a
GVHD
-SSc model and suggest that inhibition of these cells could offer therapeutic benefit for SSc.
...
PMID:T follicular helper-like cells contribute to skin fibrosis. 2962 72
