title: Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response.
abstract: Program death-1 (PD-1) is a co-inhibitory receptor inducibly expressed on activated T cells. PD-1 has been reported to be associated with the development of several autoimmune diseases including rheumatoid arthritis, but the precise cellular and molecular mechanisms have not been fully elucidated. To study the role of PD-1 in the pathogenesis of rheumatoid arthritis and the possible underlying mechanisms, we performed collagen-induced arthritis (CIA) in C57BL/6 mice. Here, we show that PD-1 deficiency leads to the development of severe CIA in mice. When analyzing T cells from CIA mice ex vivo, we noticed aberrant antigen-specific Th17 responses in mice lacking PD-1. This is possibly due to deregulated activation of PKC-θ and Akt. In support of this notion, treating Pdcd1 (-/-) mice with an inhibitor of PI3-kinase that is upstream of PKC-θ and Akt significantly suppressed the disease severity. Therefore, our data indicate that PD-1 dampens antigen-specific Th17 response, thus inhibiting the disease.
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.|Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Lifen
authors.initials: L
authors.lastname: Yang
authors.affiliation: Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Guilin
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Yassir
authors.initials: Y
authors.lastname: Hassan
authors.affiliation: Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Physiology, Xiangya Medical School, Central South University, Hunan, 410008, People's Republic of China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China. yf2323@hotmail.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.affiliation: Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA. jian.zhang@osumc.edu.|Department of Microbial Infection and Immunity, The Ohio State University, 784 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH, 43210, USA. jian.zhang@osumc.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000378:metabolism; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology*
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases
keywords: Akt; Collagen-induced arthritis; PI3-kinase; Program death-1; Th17