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Cellular and Molecular Life Sciences

, Volume 70, Issue 19, pp 3571–3589 | Cite as

O death where is thy sting? Immunologic tolerance to apoptotic self

  • Buvana Ravishankar
  • Tracy L. McGahaEmail author
Review

Abstract

In higher organisms, innate scavenging cells maintain physiologic homeostasis by removal of the billions of apoptotic cells generated on a daily basis. Apoptotic cell removal requires efficient recognition and uptake by professional and non-professional phagocytic cells, which are governed by an array of soluble and apoptotic cell-integral signals resulting in immunologically silent clearance. While apoptosis is associated with profound suppression of adaptive and innate inflammatory immunity, we have only begun to scratch the surface in understanding how immunologic tolerance to apoptotic self manifest at either the molecular or cellular level. In the last 10 years, data has emerged implicating professional phagocytes, most notably stromal macrophages and CD8α+CD103+ dendritic cells, as critical in initiation of the regulatory cascade that will ultimately lead to long-term whole-animal immune tolerance. Importantly, recent work by our lab and others has shown that alterations in apoptotic cell perception by the innate immune system either by removal of critical phagocytic sentinels in secondary lymphoid organs or blockage of immunosuppressive pathways leads to pronounced inflammation with a breakdown of tolerance towards self. This challenges the paradigm that apoptotic cells are inherently immunosuppressive, suggesting that apoptotic cell tolerance is a “context-dependent” event.

Keywords

Tolerance Macrophage Apoptosis Indoleamine 2,3 dioxygenase Marginal zone Autoimmunity 

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  1. 1.Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer CenterGeorgia Regents UniversityAugustaUSA
  2. 2.Section of Nephrology, Department of Medicine, Medical College of GeorgiaGeorgia Regents UniversityAugustaUSA

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