Reduced T cell-dependent humoral immune response in microsomal prostaglandin E synthase-1 null mice is mediated by nonhematopoietic cells.
Reduced T cell-dependent humoral immune response in microsomal prostaglandin E synthase-1 null mice is mediated by nonhematopoietic cells.
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DOI：
10.4049/jimmunol.1301942
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发表时间：
2013-11-15
期刊：
影响因子：
--
通讯作者：
Crofford LJ
中科院分区：
文献类型：
--
作者：
Kojima F;Frolov A;Matnani R;Woodward JG;Crofford LJ
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme that specifically catalyzes the conversion of prostaglandin (PG)H2 to PGE2. We showed that mPGES-1 null mice had a significantly reduced incidence and severity of collagen-induced arthritis (CIA) compared to wild-type (WT) mice associated with a marked reduction in antibodies to type II collagen. In the present study, we further elucidated the role of mPGES-1 in the humoral immune response. Basal levels of serum IgM and IgG were significantly reduced in mPGES-1 null mice. Compared with WT mice, mPGES-1 null mice exhibited a significant reduction of hapten-specific serum antibodies in response to immunization with the T-cell dependent antigen DNP-KLH. Immunization with the T-cell independent type-1 antigen TNP-LPS or the T-cell independent type-2 antigen DNP-Ficoll revealed minimal differences between strains. Germinal center formation in the spleens of mPGES-1 null and WT mice were similar after immunization with DNP-KLH. To determine if the effect of mPGES-1 and PGE2 was localized to hematopoietic or non-hematopoietic cells, we generated bone marrow chimeras. We demonstrated that mPGES-1 deficiency in non-hematopoietic cells was the critical factor for reduced T-cell dependent antibody production. We conclude that mPGES-1 and PGE2-dependent phenotypic changes of non-hematopoietic/mesenchymal stromal cells play a key role in T-cell dependent humoral immune responses in vivo. These findings may have relevance to the pathogenesis of rheumatoid arthritis and other autoimmune inflammatory diseases associated with autoantibody formation.
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影响因子：
3.7
作者：
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通讯作者：
Crofford, LJ
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