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Peroxisome proliferator-activated receptor-γ haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis

By Keigo Setoguchi, Yoshikata Misaki, Yasuo Terauchi, Toshimasa Yamauchi, Kimito Kawahata, Takashi Kadowaki and Kazuhiko Yamamoto

Abstract

Peroxisome proliferator–activated receptor-γ (PPARγ) controls adipogenesis and glucose metabolism. It was reported recently that PPARγ activation by its agonistic ligands modifies lymphocyte function. Since synthetic ligands are known to exert their effect via PPARγ-dependent and -independent pathways, we examined the physiological role of PPARγ in lymphocytes by using heterozygote mutant mice in which one allele of PPARγ is deleted (PPARγ+/–). In contrast to T cells, which did not exhibit a significant difference, B cells from PPARγ+/– showed an enhanced proliferative response to stimulation by either lipopolysaccharide or cross-linking of antigen receptors. Dysregulation of the NF-κB pathway in B cells from PPARγ+/– was indicated by spontaneous NF-κB activation, as well as increased IκBα phosphorylation and gel-shift activity following LPS stimulation. Mice primed with either ovalbumin or methylated BSA also showed enhanced antigen-specific immune response of both T and B cells, an immunological abnormality that exacerbated antigen-induced arthritis. These findings indicate that PPARγ plays a critical role in the control of B cell response and imply a role in diseases in which B cell hyperreactivity is involved, such as arthritis and autoimmunity

Topics: Article
Publisher: American Society for Clinical Investigation
Year: 2001
OAI identifier: oai:pubmedcentral.nih.gov:200985
Provided by: PubMed Central
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