Regulation of cytokine production during phagocytosis of apoptotic cells

Elaine Y. L. Chung, Jung Kim Sun, Jing Ma Xiao

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic cells would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The IL-12 family of cytokines (IL-12, IL-23, and IL-27) and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells (APCs) and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro- and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein (GC-BP), through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.

Original languageEnglish (US)
Pages (from-to)154-161
Number of pages8
JournalCell Research
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Fingerprint

Cytophagocytosis
Cytokines
Interleukin-12
Phagocytes
Antigen-Presenting Cells
Lymphocytes
Interleukin-10
Interleukin-27
Macrophages
Interleukin-23
Self Tolerance
Autoimmunity
Systemic Lupus Erythematosus
Autoimmune Diseases
Tyrosine
Rheumatoid Arthritis
Carrier Proteins
Anti-Inflammatory Agents
Eating
Apoptosis

Keywords

  • Apoptotic cells
  • Autoimmunity
  • Cytokines
  • Phagocytosis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Regulation of cytokine production during phagocytosis of apoptotic cells. / Chung, Elaine Y. L.; Sun, Jung Kim; Xiao, Jing Ma.

In: Cell Research, Vol. 16, No. 2, 01.02.2006, p. 154-161.

Research output: Contribution to journalArticle

Chung, Elaine Y. L. ; Sun, Jung Kim ; Xiao, Jing Ma. / Regulation of cytokine production during phagocytosis of apoptotic cells. In: Cell Research. 2006 ; Vol. 16, No. 2. pp. 154-161.
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