Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen

Tracy L. McGaha, Yunying Chen, Buvana Ravishankar, Nico Van Rooijen, Mikael C.I. Karlsson

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Marginal zone macrophages (MZMs) are a small subset of specialized splenic macrophages known to interact with apoptotic material entering the spleen from circulation. To evaluate whether MZMs regulate immunity to apoptotic material we depleted MZMs and assessed innate and adaptive immune responses to apoptotic cells administered systemically. MZM depletion altered the spatial localization of apoptotic cells, which accumulated in T-cell areas of the lymphoid follicles. MZM depletion also enhanced phagocytosis of apoptotic cells by red pulp (CD68+F4/80+) macrophages, which expressed increased CD86, MHCII, and CCR7. MZM depletion led to increased production of proinflammatory cytokines and enhanced lymphocyte responsiveness to apoptotic cell antigens. Furthermore, we found that MZM depletion accelerated autoimmune disease progression in mice genetically prone to systemic lupus erythematosus and caused significant mortality in wild-type mice repeatedly exposed to exogenous apoptotic thymocytes. These findings support the hypothesis that MZMs are central in the clearance of apoptotic cells to minimize the immunogenicity of autoantigens.

Original languageEnglish (US)
Pages (from-to)5403-5412
Number of pages10
JournalBlood
Volume117
Issue number20
DOIs
StatePublished - May 19 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    McGaha, T. L., Chen, Y., Ravishankar, B., Rooijen, N. V., & Karlsson, M. C. I. (2011). Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood, 117(20), 5403-5412. https://doi.org/10.1182/blood-2010-11-320028