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IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells
and Restraining Autoantibody Production in Congenic Lupus-Prone Mice
#MMPMID26964093
Baglaenko Y
; Manion KP
; Chang NH
; Gracey E
; Loh C
; Wither JE
PLoS One
2016[]; 11
(3
): e0150515
PMID26964093
show ga
The development and progression of systemic lupus erythematosus is mediated by
the complex interaction of genetic and environmental factors. To decipher the
genetics that contribute to pathogenesis and the production of pathogenic
autoantibodies, our lab has focused on the generation of congenic lupus-prone
mice derived from the New Zealand Black (NZB) strain. Previous work has shown
that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion
of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when
crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B
cells but not NKT cells derived from these mice could suppress the development of
pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics
that leads to expansion of these two innate-like populations through the creation
of additional sub-congenic mice and to characterize the role of IL-10 in the
suppression of autoimmunity through the generation of IL-10 knockout mice. We
show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4
interval spanning 91 to 123 Mb, which is distinct from the region that mediates
the majority of the suppressive phenotype. We also demonstrate that IL-10 is
critical to restraining autoantibody production and surprisingly plays a vital
role in supporting the expansion of innate-like populations.
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