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Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity

Journal

IMMUNOLOGICAL REVIEWS
Volume 269, Issue 1, Pages 26-43

Publisher

WILEY
DOI: 10.1111/imr.12382

Keywords

apoptosis; macrophage; tolerance; autoimmunity; marginal zone; B cell

Categories

Funding

  1. NIH [R01AR067763, R01CA190449, R21AI105500]
  2. lupus research institute (TLM)
  3. Swedish Research Council
  4. Magnus Bergvall Foundation
  5. Swedish Medical Society
  6. Swedish Rheumatic Foundation
  7. King Gustav V 80-year Foundation
  8. Torsten Soderberg Foundation
  9. Cardiovascular Research Programme (MCIK)
  10. NATIONAL CANCER INSTITUTE [R01CA190449] Funding Source: NIH RePORTER
  11. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI105500] Funding Source: NIH RePORTER
  12. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR067763] Funding Source: NIH RePORTER

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Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.

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