2013年11月
Reduced T Cell-Dependent Humoral Immune Response in Microsomal Prostaglandin E Synthase-1 Null Mice Is Mediated by Nonhematopoietic Cells
JOURNAL OF IMMUNOLOGY
- ,
- ,
- ,
- ,
- 巻
- 191
- 号
- 10
- 開始ページ
- 4979
- 終了ページ
- 4988
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.4049/jimmunol.1301942
- 出版者・発行元
- AMER ASSOC IMMUNOLOGISTS
Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that specifically catalyzes the conversion of PGH(2) to PGE(2). We showed that mPGES-1 null mice had a significantly reduced incidence and severity of collagen-induced arthritis compared with wild-type (WT) mice associated with a marked reduction in Abs to type II collagen. In this 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 Abs in response to immunization with the T cell-dependent (TD) Ag DNP-keyhole limpet hemocyanin. Immunization with the T cell-independent type 1 Ag trinitrophenyl-LPS or the T cell-independent type 2 Ag DNP-Ficoll revealed minimal differences between strains. Germinal center formation in the spleen of mPGES-1 null and WT mice were similar after immunization with DNP-keyhole limpet hemocyanin. To determine whether the effect of mPGES-1 and PGE2 was localized to hematopoietic or nonhematopoietic cells, we generated bone marrow chimeras. We demonstrated that mPGES-1 deficiency in nonhematopoietic cells was the critical factor for reduced TD Ab production. We conclude that mPGES-1 and PGE(2)-dependent phenotypic changes of nonhematopoietic/mesenchymal stromal cells play a key role in TD 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.
- リンク情報
- ID情報
-
- DOI : 10.4049/jimmunol.1301942
- ISSN : 0022-1767
- eISSN : 1550-6606
- Web of Science ID : WOS:000326584600012