title: Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen.
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.
authors: Department of Medicine, Immunotherapy Center, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 30912, USA. tmcgaha@georgiahealth.edu
authors: Tracy L
authors: TL
authors: McGaha
authors: Yunying
authors: Y
authors: Chen
authors: Buvana
authors: B
authors: Ravishankar
authors: Nico
authors: N
authors: van Rooijen
authors: Mikael C I
authors: MC
authors: Karlsson
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D051940:B7-2 Antigen / Q000378:metabolism; D004002:Clodronic Acid / Q000008:administration & dosage; D005260:Female; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology* / Q000276:immunology*
chemical_list: D001324:Autoantigens; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D004002:Clodronic Acid