Macrophage scavenger receptor 1 (Msr1, SR-A) Influences b cell autoimmunity by regulating soluble autoantigen concentration

Stefanie Haasken, Jennifer L. Auger, Justin J. Taylor, Patricia M. Hobday, Brian D. Goudy, Philip J. Titcombe, Daniel L. Mueller, Bryce A. Binstadt

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The class A macrophage scavenger receptor Msr1 (SR-A, CD204) has been reported to participate in the maintenance of immunological tolerance. We investigated the role of Msr1 in a mouse model of autoantibody-dependent arthritis. Genetic deficiency of Msr1 in K/BxN TCR transgenic mice decreased the incidence and severity of arthritis because of decreased autoantibody production. Despite normal initial activation of autoreactive CD4+ T cells, potentially autoreactive B cells in Msr1+/+ K/BxN mice retained a naive phenotype and did not expand. This was not due to an intrinsic B cell defect. Rather, we found that macrophages lacking Msr1 were inefficient at taking up the key autoantigen glucose-6-phosphate isomerase and that Msr1- deficient mice had elevated serum concentrations of glucose-6-phosphate isomerase. Arthritis developed normally when bone marrow from Msr1+/+ K/BxN mice was transplanted into hosts whose macrophages did express Msr1. Thus, Msr1 can regulate the concentration of a soluble autoantigen. In this model, the absence of Msr1 led to higher levels of soluble autoantigen and protected mice from developing pathogenic autoantibodies, likely because of altered cognate interactions of autoreactive T and B cells with impaired differentiation of follicular Th cells.

Original languageEnglish (US)
Pages (from-to)1055-1062
Number of pages8
JournalJournal of Immunology
Volume191
Issue number3
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Haasken, S., Auger, J. L., Taylor, J. J., Hobday, P. M., Goudy, B. D., Titcombe, P. J., Mueller, D. L., & Binstadt, B. A. (2013). Macrophage scavenger receptor 1 (Msr1, SR-A) Influences b cell autoimmunity by regulating soluble autoantigen concentration. Journal of Immunology, 191(3), 1055-1062. https://doi.org/10.4049/jimmunol.1201680