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

Buvana Ravishankar, Tracy L. McGaha

Research output: Contribution to journalReview article

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3571-3589
Number of pages19
JournalCellular and Molecular Life Sciences
Volume70
Issue number19
DOIs
StatePublished - Oct 1 2013

Keywords

  • Apoptosis
  • Autoimmunity
  • Indoleamine 2,3 dioxygenase
  • Macrophage
  • Marginal zone
  • Tolerance

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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