Interleukin-10 Expression in Macrophages during Phagocytosis of Apoptotic Cells Is Mediated by Homeodomain Proteins Pbx1 and Prep-1

Elaine Y. Chung, Jianguo Liu, Yoichiro Homma, Yunhua Zhang, Andrea Brendolan, Matilde Saggese, Jihong Han, Roy Silverstein, Licia Selleri, Xiaojing Ma

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Production of interleukin (IL)-10, a major immunoregulatory cytokine, by phagocytes during clearance of apoptotic cells is critical to ensuring cellular homeostasis and suppression of autoimmunity. Little is known about the regulatory mechanisms in this fundamental process. We report that IL-10 production stimulated by apoptotic cells was regulated at the point of transcription in a manner dependent on p38 mitogen-activated protein kinase, partially on the scavenger receptor CD36, and required cell-cell contact but not phagocytosis. By using a reporter assay, we mapped the apoptotic-cell-response element (ACRE) in the human IL10 promoter and provide biochemical and physiological evidence that ACRE mediates the transcriptional activation of IL10 by pre-B cell leukemia transcription factor-1b and another Hox cofactor Pbx-regulating protein 1 in response to apoptotic cells. This study establishes a role of two developmentally critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the immune system.

Original languageEnglish (US)
Pages (from-to)952-964
Number of pages13
JournalImmunity
Volume27
Issue number6
DOIs
StatePublished - Dec 21 2007

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Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Chung, E. Y., Liu, J., Homma, Y., Zhang, Y., Brendolan, A., Saggese, M., Han, J., Silverstein, R., Selleri, L., & Ma, X. (2007). Interleukin-10 Expression in Macrophages during Phagocytosis of Apoptotic Cells Is Mediated by Homeodomain Proteins Pbx1 and Prep-1. Immunity, 27(6), 952-964. https://doi.org/10.1016/j.immuni.2007.11.014