Paradoxical effects of all-trans-retinoic acid on lupus-like disease in the MRL/lpr mouse model

PloS One
Xiaofeng LiaoXin M Luo

Abstract

Roles of all-trans-retinoic acid (tRA), a metabolite of vitamin A (VA), in both tolerogenic and immunogenic responses are documented. However, how tRA affects the development of systemic autoimmunity is poorly understood. Here we demonstrate that tRA have paradoxical effects on the development of autoimmune lupus in the MRL/lpr mouse model. We administered, orally, tRA or VA mixed with 10% of tRA (referred to as VARA) to female mice starting from 6 weeks of age. At this age, the mice do not exhibit overt clinical signs of lupus. However, the immunogenic environment preceding disease onset has been established as evidenced by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and dendritic cells in secondary lymphoid organs. After 8 weeks of tRA, but not VARA treatment, significantly higher pathological scores in the skin, brain and lung were observed. These were accompanied by a marked increase in B-cell responses that included autoantibody production and enhanced expression of plasma cell-promoting cytokines. Paradoxically, the number of lymphocytes in the mesenteric lymph node decreased with tRA that led to significantly reduced lymphadenopathy. In addition, tRA differentially affected renal pathology, in...Continue Reading

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Citations

Apr 2, 2016·Journal of Immunology Research·Xiaofeng LiaoXin M Luo
Dec 10, 2015·Frontiers in Immunology·Qinghui MuXin M Luo
Jun 17, 2016·Nature Reviews. Rheumatology·Tom Van de WieleDirk Elewaut
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May 10, 2016·Arthritis & Rheumatology·Shuo WeiKun Ping Lu
Oct 24, 2017·Scientific Reports·Qinghui MuXin M Luo
Oct 9, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaofeng LiaoXin M Luo
Jul 13, 2017·Microbiome·Qinghui MuXin M Luo
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Dec 3, 2020·Frontiers in Nutrition·Hanchang HeYuqiang Nie

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Methods Mentioned

BETA
ELISA
PCR
Ultra Performance Liquid Chromatography
flow cytometry

Software Mentioned

Olympus
ElementsD
NIS
Stereo Investigator
Chemstrip
cellSens

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