Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response

Lifen Yang; Guilin Qiao; Yassir Hassan; Zhenping Li; Xiaoqing Zhang; Huimin Kong; Weimin Zeng; Fei Yin; Jian Zhang

doi:10.1007/s00005-016-0404-z

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Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response

Journal article

Open access

Peer reviewed

Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response

Lifen Yang, Guilin Qiao, Yassir Hassan, Zhenping Li, Xiaoqing Zhang, Huimin Kong, Weimin Zeng, Fei Yin and Jian Zhang

Archivum Immunologiae et Therapiae Experimentalis, Vol.64(5), pp.417-423

10/2016

DOI: 10.1007/s00005-016-0404-z

PMCID: PMC5500291

PMID: 27197661

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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.

Phosphorylation

Flow Cytometry

Cell Differentiation

Arthritis - metabolism

Lymphocyte Activation

Humans

Mice, Inbred C57BL

Autoimmune Diseases - immunology

Programmed Cell Death 1 Receptor - metabolism

Collagen - chemistry

Male

Mice, Transgenic

Phosphatidylinositol 3-Kinases - metabolism

Arthritis, Experimental

Arthritis, Rheumatoid - metabolism

Animals

Arthritis - immunology

Th17 Cells - cytology

Mice

Arthritis, Rheumatoid - immunology

Autoimmune Diseases - metabolism

Disease Models, Animal

Details

Title: Subtitle: Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response
Creators: Lifen Yang - Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA
Guilin Qiao - Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA
Yassir Hassan - Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA
Zhenping Li - Section of Nephrology, Department of Medicine, The Committees on Immunology and Molecular Medicine, The University of Chicago, Chicago, IL, 60637, USA
Xiaoqing Zhang - Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China
Huimin Kong - Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China
Weimin Zeng - Department of Physiology, Xiangya Medical School, Central South University, Hunan, 410008, People's Republic of China
Fei Yin - Department of Pediatrics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, People's Republic of China. yf2323@hotmail.com
Jian Zhang - 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
Resource Type: Journal article
Publication Details: Archivum Immunologiae et Therapiae Experimentalis, Vol.64(5), pp.417-423
DOI: 10.1007/s00005-016-0404-z
PMID: 27197661
PMCID: PMC5500291
NLM abbreviation: Arch Immunol Ther Exp (Warsz)
ISSN: 0004-069X
eISSN: 1661-4917
Publisher: Switzerland
Grant note: R01 AI090901 / NIAID NIH HHS R01 AR049775 / NIAMS NIH HHS
Language: English
Date published: 10/2016
Academic Unit: Pathology
Record Identifier: 9984047622902771

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