Summary
RORγt+Foxp3+ regulatory T (Treg)
cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset
of Treg cells, which have the potential to regulate the development of
experimental autoimmune encephalomyelitis (EAE) thorough a specific
repression of T helper 17 (Th17) cell mediated inflammation. However,
the function of Tr17 cells the development of other autoimmune diseases
such as autoimmune arthritis remains unclear. Collagen induced arthritis
(CIA) was found to be prolonged in
Foxp3creRORγtfl/fl mice, in which
Tr17 cells were deleted, compared with
Foxp3wtRORγtfl/fl mice. Tr17 cells
were significantly increased in ankle joints compared with draining
lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6)
was up-regulated on Tr17 cells compared to RORγt negative Treg cells.
CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced
TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS)
expression was also up-regulated on Tr17 cells compared to RORγt
negative Treg cells. IL-10-producing cells and
Blimp-1+ cells were increased in Tr17 cells compared
to RORγt-Treg cells. Tr17-enriched Treg cells
significantly suppressed proliferation of conventional T cells compared
with CCR6-Treg cells. Tr17 cells increased during the
clinical course of CIA and accumulated in inflamed joints. These cells
expressed CD25, CTLA4, GITR, and ICOS molecules and up-regulated Blimp-1
and over-produced IL-10. Moreover, CCR6+ Treg cells
significantly suppressed cell proliferation. Taken together, it appears
that Tr17 cells play a crucial role in the regulation of autoimmune
arthritis.