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B cells expressing IFN-? suppress Treg-cell differentiation and promote
autoimmune experimental arthritis
#MMPMID25645456
Olalekan SA
; Cao Y
; Hamel KM
; Finnegan A
Eur J Immunol
2015[Apr]; 45
(4
): 988-98
PMID25645456
show ga
Clinical efficacy in the treatment of rheumatoid arthritis with anti-CD20
(Rituximab)-mediated B-cell depletion has garnered interest in the mechanisms by
which B cells contribute to autoimmunity. We have reported that B-cell depletion
in a murine model of proteoglycan-induced arthritis (PGIA) leads to an increase
in Treg cells that correlate with decreased autoreactivity. Here, we demonstrate
that the increase in Treg cells after B-cell depletion is due to an increase in
the differentiation of naïve CD4(+) T cells into Treg cells. Since the
development of PGIA is dependent on IFN-? and B cells are reported to produce
IFN-?, we hypothesized that B-cell-specific IFN-? plays a role in the development
of PGIA. Accordingly, mice with B-cell-specific IFN-? deficiency were as
resistant to the induction of PGIA as mice that were completely IFN-? deficient.
Importantly, despite a normal frequency of IFN-?-producing CD4(+) T cells,
B-cell-specific IFN-?-deficient mice exhibited a higher percentage of Treg cells
compared with that in WT mice. These data indicate that B-cell IFN-? production
inhibits Treg-cell differentiation and exacerbates arthritis. Thus, we have
established that IFN-?, specifically derived from B cells, uniquely contributes
to the pathogenesis of autoimmunity through prevention of immunoregulatory
mechanisms.
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