title: PILRα negatively regulates mouse inflammatory arthritis.
abstract: Paired Ig-like type 2 receptor (PILR)α inhibitory receptor and its counterpart PILRβ activating receptor are coexpressed on myeloid cells. In this article, we report that PILRα, but not PILRβ, is elevated in human rheumatoid arthritis synovial tissue and correlates with inflammatory cell infiltration. Pilrα(-/-) mice produce more pathogenic cytokines during inflammation and are prone to enhanced autoimmune arthritis. Correspondingly, engaging PILRα with anti-PILRα mAb ameliorates inflammation in mouse arthritis models and suppresses the production of proinflammatory cytokines. Our studies suggest that PILRα mediates an important inhibitory pathway that can dampen inflammatory responses.
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology, Genentech, South San Francisco, CA 94080;
authors.forename: Patrick
authors.initials: P
authors.lastname: Caplazi
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Protein Chemistry, Genentech, South San Francisco, CA 94080;
authors.forename: Anita
authors.initials: A
authors.lastname: Mazloom
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080;
authors.forename: Sarah
authors.initials: S
authors.lastname: Kummerfeld
authors.affiliation: Department of Protein Chemistry, Genentech, South San Francisco, CA 94080;
authors.forename: Gabriel
authors.initials: G
authors.lastname: Quinones
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Kate
authors.initials: K
authors.lastname: Senger
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Justin
authors.initials: J
authors.lastname: Lesch
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Ivan
authors.initials: I
authors.lastname: Peng
authors.affiliation: Department of Antibody Engineering, Genentech, South San Francisco, CA 94080;
authors.forename: Andrew
authors.initials: A
authors.lastname: Sebrell
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA 94080;
authors.forename: Wilman
authors.initials: W
authors.lastname: Luk
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA 94080;
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Biomedical Imaging, Genentech, South San Francisco, CA 94080;
authors.forename: Kai
authors.initials: K
authors.lastname: Barck
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA 94080;
authors.forename: Judy
authors.initials: J
authors.lastname: Young
authors.affiliation: Department of Transgenic Technology, Genentech, South San Francisco, CA 94080;
authors.forename: Mariela
authors.initials: M
authors.lastname: Del Rio
authors.affiliation: Department of Microbial Pathogenesis, Genentech, South San Francisco, CA 94080; and.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lehar
authors.affiliation: Department of Transgenic Technology, Genentech, South San Francisco, CA 94080;
authors.forename: Vida
authors.initials: V
authors.lastname: Asghari
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: WeiYu
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Microbial Pathogenesis, Genentech, South San Francisco, CA 94080; and.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mariathasan
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Jason
authors.initials: J
authors.lastname: DeVoss
authors.affiliation: Department of Early Stage Cell Culture, Genentech, South San Francisco, CA 94080.
authors.forename: Shahram
authors.initials: S
authors.lastname: Misaghi
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Mercedesz
authors.initials: M
authors.lastname: Balazs
authors.affiliation: Department of Antibody Engineering, Genentech, South San Francisco, CA 94080;
authors.forename: Tao
authors.initials: T
authors.lastname: Sai
authors.affiliation: Department of Protein Chemistry, Genentech, South San Francisco, CA 94080;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haley
authors.affiliation: Department of Protein Chemistry, Genentech, South San Francisco, CA 94080;
authors.forename: Philip E
authors.initials: PE
authors.lastname: Hass
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Flavius
authors.initials: F
authors.lastname: Martin
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080;
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080; zarrin.ali@gene.com.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Zarrin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006614:Hindlimb / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C548037:PILRalpha protein, mouse; D011971:Receptors, Immunologic