title: LILRA5 is expressed by synovial tissue macrophages in rheumatoid arthritis, selectively induces pro-inflammatory cytokines and IL-10 and is regulated by TNF-alpha, IL-10 and IFN-gamma.
abstract: Leukocyte immunoglobulin-like receptor A5 (LILRA5) belongs to a family of receptors known to regulate leukocyte activation. There are two membrane-bound and two soluble forms of LILRA5. The transmembrane LILRA5 contain a short cytoplasmic domain and a charged arginine residue within the transmembrane region. Cross-linking of LILRA5 on monocytes induced production of pro-inflammatory cytokines, suggesting that LILRA5 plays a role in inflammation. However, expression of LILRA5 in diseases with extensive inflammatory component is unknown. Rheumatoid arthritis (RA) is a chronic inflammatory synovitis characterized by unregulated activation of leukocytes leading to joint destruction. Here we demonstrate extensive LILRA5 expression on synovial tissue macrophages and in synovial fluid of patients with active RA but not in patients with osteoarthritis. We also show that LILRA5 associated with the common gamma chain of the FcR and LILRA5 cross-linking induced phosphorylation of Src tyrosine kinases and Spleen tyrosine kinase (Syk). Furthermore, LILRA5 induced selective production of pro-inflammatory cytokines as well as IL-10. LILRA5 mRNA and protein expression was tightly regulated by TNF-alpha, IL-10 and IFN-gamma. Increased expression of LILRA5 in rheumatoid tissue, together with its ability to induce key cytokines involved in RA, suggests that this novel receptor may contribute to disease pathogenesis.
authors.affiliation: Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Ainslie
authors.initials: A
authors.lastname: Mitchell
authors.forename: Carles
authors.initials: C
authors.lastname: Rentero
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Endoh
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hsu
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.forename: Carolyn
authors.initials: C
authors.lastname: Geczy
authors.forename: H Patrick
authors.initials: HP
authors.lastname: McNeil
authors.forename: Luis
authors.initials: L
authors.lastname: Borges
authors.forename: Nicodemus
authors.initials: N
authors.lastname: Tedla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C471973:LILRA5 protein, human; D011971:Receptors, Immunologic; D011505:Protein-Tyrosine Kinases