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2014 ; 2
(ä): 14038
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Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the
development of collagen-induced arthritis
#MMPMID26097753
Yuan X
; Garrett-Sinha LA
; Sarkar D
; Yang S
Bone Res
2014[]; 2
(ä): 14038
PMID26097753
show ga
IFT20 is the smallest member of the intraflagellar transport protein (IFT)
complex B. It is involved in cilia formation. Studies of IFT20 have been confined
to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated
T cells and have functions in immune synapse formation and signaling in vitro.
However, how IFT20 regulates T-cell development and activation in vivo is still
unknown. We deleted the IFT20 gene in early and later stages of T-cell
development by crossing IFT20(flox/flox) (IFT20(f/f) ) mice with Lck-Cre and
CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation
and in the development of T cell-mediated collagen-induced arthritis (CIA). We
found that both Lck-Cre/IFT20(f/f) and CD4-Cre/IFT20(f/f) mice were
indistinguishable from their wild-type littermates in body size, as well as in
the morphology and weight of the spleen and thymus. However, the number of CD4-
and CD8-positive cells was significantly lower in thymus and spleen in
Lck-Cre/IFT20(f/f) mice. Meanwhile, the incidence and severity of CIA symptoms
were significantly decreased, and inflammation in the paw was significantly
inhibited in Lck-Cre/IFT20(f/f) mice compared to Lck-Cre/IFT20(+/+) littermates.
Deletion IFT20 in more mature T cells of CD4-Cre/IFT20(f/f) mice had only mild
effects on the development of T cells and CIA. The expression of IL-1?, IL-6 and
TGF-?1 were significantly downregulated in the paw of Lck-Cre/IFT20(f/f) mice,
but just slight decreased in CD4-Cre/IFT20(f/f) mice. These results demonstrate
that deletion of IFT20 in the early stage of T-cell development inhibited CIA
development through regulating T-cell development and the expression of critical
cytokines.