Genetic dissection of a major haplotype associated with arthritis reveal FcγR2b and FcγR3 to act additively. Issue 3 (10th December 2020)

• Record Type: Journal Article
• Authors: Vaartjes, Daniëlle; Klaczkowska, Dorota; Cragg, Mark S; Nandakumar, Kutty Selva; Bäckdahl, Liselotte; Holmdahl, Rikard
• Is Part Of: European journal of immunology. Volume 51:Issue 3(2021)
• Page Start: 682
• Page End: 693
• Publication Date: 2020-12-10
• Subjects: collagen‐induced arthritis -- Fc gamma receptor -- Cia9 locus -- FcγR2b -- FcγR3; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048605
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: A haplotype with tightly linked Fc gamma receptor (FcγR) genes is known as a major locus controlling immune responses and autoimmune diseases, including arthritis. Here, we split a congenic fragment derived from the NOD mouse ( Cia9 ) to study its effect on immune response and arthritis in mice. We found that arthritis susceptibility was indeed controlled by the FcγR gene cluster and a recombination between the Fcγ R2b and Fcγ R3 loci gave us the opportunity to separately study their impact. We identified the NOD‐derived Fcγ R2b and Fcγ R3 alleles as disease‐promoting for arthritis development without impact on antibody secretion. We further found that macrophage‐mediated phagocytosis was directly correlated to Fcγ R3 expression in the congenic mice. In conclusion, we positioned Fcγ R2b and Fcγ R3 alleles as disease regulatory and showed that their genetic polymorphisms independently and additively control innate immune cell activation and arthritis. Abstract : The closely linked polymorphic Fcgr2b and Fcgr3 NOD alleles promote the development of arthritis and enhance the inflammatory response capacity.