Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of col agen-induced arthritis

作     者：Xue Yuan Lee Ann Garrett-Sinha Debanjan Sarkar Shuying Yang 

作者机构：Department of Oral BiologySchool of Dental MedicineUniversity at BuffaloThe State University of New YorkBuffaloNY 14214USA Department of BiochemistrySchool of Medicine and Biomedical SciencesUniversity at BuffaloThe State University of New YorkBuffaloNY 14203USA Laboratory for Biomaterials and Regenerative TherapeuticsDepartment of Biomedical EngineeringUniversity at BuffaloThe State University of New YorkBuffaloNY 14260-2050USA Developmental Genomics GroupNew York State Center of Excellence in Bioinformatics and Life SciencesUniversity at BuffaloThe State University of New YorkBuffaloNY 14203USA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2014年第2卷第4期

页      面：241-251页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases part of the National Institutes of Health under Award Numbers AR055678 DE023105 and AR061052 to SY 

主　　题：INTRAFLAGELLAR TRANSPORT IFT NF-KAPPA-B RHEUMATOID-ARTHRITIS CELL DEVELOPMENT PRIMARY CILIUM KINESIN-II MICE EXPRESSION COMPLEX PROTEINS 

摘      要：IFT20 is the smallest member of the intraflagellar transport protein（IFT） complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20flox/flox（IFT20f/f） mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis（CIA）. We found that both Lck-Cre/IFT20f/f and CD4-Cre/IFT20f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20f/f mice compared to Lck-Cre/IFT201/1littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1b, IL-6 and TGF-b1 were significantly downregulated in the paw of Lck-Cre/IFT20f/f mice, but just slight decreased in CD4-Cre/IFT20f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.