Publisher： John Wiley & Sons Inc
E-ISSN： 2326-5205|66|4|852-862
ISSN： 2326-5191
Source： ARTHRITIS & RHEUMATOLOGY, Vol.66, Iss.4, 2014-04, pp. : 852-862
Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.
Abstract
ObjectiveArthritis and valvular carditis coexist in several human rheumatic diseases, including systemic lupus erythematosus, rheumatic fever, and rheumatoid arthritis. T cell receptor–transgenic K/BxN mice develop spontaneous autoantibody‐associated arthritis and valvular carditis. The common Fc receptor γ (FcRγ) signaling chain is required for carditis to develop in K/BxN mice. FcRγ pairs with numerous receptors in a variety of cells. The aim of this study was to identify the FcRγ‐associated receptors and Fcγ receptor (FcγR)–expressing cells that mediate valvular carditis in this model.MethodsWe bred K/BxN mice lacking the genes that encode activating Fcγ receptors (FcγRI, FcγRIII, and FcγRIV), and we assessed these mice for valvular carditis. We similarly evaluated complement component C3–deficient K/BxN mice. Immunohistochemistry, bone marrow transplantation, and macrophage depletion were used to define the key FcRγ‐expressing cell type.ResultsGenetic deficiency of only one of the activating Fcγ receptors did not prevent carditis, whereas deficiency of all 3 activating Fcγ receptors did. Further analysis demonstrated that FcγRIII and FcγRIV were the key drivers of valve inflammation; FcγRI was dispensable. C3 was not required. FcRγ expression by radioresistant cells was critical for valvular carditis to develop, and further analysis indicated that macrophages were the key candidate FcγR‐expressing effectors of carditis.ConclusionFcγRIII and FcγRIV act redundantly to promote valvular carditis in K/BxN mice with systemic autoantibody‐associated arthritis. Macrophage depletion reduced the severity of valve inflammation. These findings suggest that pathogenic autoantibodies engage Fcγ receptors on macrophages to drive valvular carditis. Our study provides new insight into the pathogenesis of cardiovascular inflammation in the setting of autoantibody‐associated chronic inflammatory diseases.
Related content
The platelet Fc receptor, FcγRIIa
IMMUNOLOGICAL REVIEWS (ELECTRONIC), Vol. 268, Iss. 1, 2015-11 ,pp. :
Access to resources
Recommend
Fcγ receptor pathways during active and passive immunization
IMMUNOLOGICAL REVIEWS (ELECTRONIC), Vol. 268, Iss. 1, 2015-11 ,pp. :
Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol. 13, Iss. 6, 2015-06 ,pp. :
The high‐affinity receptor for IgG, FcγRI, of humans and non‐human primates
IMMUNOLOGICAL REVIEWS (ELECTRONIC), Vol. 268, Iss. 1, 2015-11 ,pp. :