title: Siglec-9 is upregulated in rheumatoid arthritis and suppresses collagen-induced arthritis through reciprocal regulation of Th17-/Treg-cell differentiation.
abstract: Sialic acid-binding Ig-like lectin-9 (Siglec-9) is a novel sialic acid-binding member of the immunoglobulin superfamily and is broadly expressed on immune cells, which can inhibit both innate and adaptive immune responses through immunoreceptor tyrosine-based inhibitory motifs. However, the exact role of Siglec-9 in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we determined soluble Siglec-9 (sSiglec-9) levels in the serum and synovial fluid of patients with RA and evaluated the relation between sSiglec-9 levels and clinical factors. In addition, we investigated whether Siglec-9 could alleviate collagen-induced arthritis (CIA) development in mice and explored the molecular mechanisms involved. The results showed that, in the serum and synovial fluid of patients with RA, sSiglec-9 levels were elevated. Thus, high sSiglec-9 serum levels associated with disease severity in patients with RA. Furthermore, administration of recombinant human Siglec-9 Fc chimera protein significantly attenuated collagen-induced arthritis development in vivo and in vitro by reciprocal regulation of the differentiation of Th17 and Treg cells. Our findings collectively indicate that Siglec-9 plays a potent immunosuppressive role in the pathogenesis of RA by reciprocal regulation of Th17-/Treg-cell differentiation. In conclusion, Siglec-9 may serve as a potential diagnostic and therapeutic target for RA.
authors.affiliation: Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Health Science Center, Xi'an Jiaotong University, Xi'an, China.|Department of Rheumatology, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Health Science Center, Xi'an Jiaotong University, Xi'an, China.|Department of Rheumatology and Immunology, Xi'an No.5 Hospital, Xi'an, Shaanxi, China.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department of Rheumatology and Immunology, Xi'an No.5 Hospital, Xi'an, Shaanxi, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Rheumatology, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.|Core Research Laboratory, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: X
authors.identifier: http://orcid.org/0000-0003-1893-7005
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China.
authors.forename: R
authors.initials: R
authors.lastname: Tu
authors.affiliation: Department of Rheumatology, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008811:Mice, Inbred DBA; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D011994:Recombinant Proteins; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins