A novel function of CXCL10 in mediating monocyte production of proinflammatory cytokines

J Leukoc Biol. 2017 Nov;102(5):1271-1280. doi: 10.1189/jlb.5A0717-302. Epub 2017 Sep 12.


IFN-γ-inducible protein 10 (CXCL10), a chemokine that is abundantly secreted in response to inflammatory stimuli, has been implicated in the pathogenesis of multiple inflammatory diseases, such as inflammatory bowel disease. Whereas CXCL10 is traditionally recognized for recruiting pathogenic T cells to inflamed sites, its nonchemotactic role during inflammation remains poorly defined. In this report, we identified a novel function of CXCL10 in the regulation of the inflammatory potential of human monocytes to produce cytokines. We found that CXCL10 was necessary and sufficient for IFN-γ-primed human monocytes to induce a robust production of proinflammatory cytokines, such as IL-12 and IL-23. CXCL10-induced monocyte production of these cytokines depended on CXCR3 receptor engagement as well as on the Iκ B kinase and p38 MAPK signaling pathways. By using an innate-mediated murine colitis model, we demonstrated that anti-CXCL10 Ab treatment robustly suppressed the local production of myeloid-derived inflammatory cytokines and intestinal tissue damage. Together, our data unravel a previously unappreciated role of CXCL10 in the amplification of myeloid cell-mediated inflammatory responses. Targeting CXCL10 is therefore an attractive approach to treating inflammatory diseases that are driven by innate and adaptive immunity.

Keywords: CXCL10; CXCR3; IFN-γ; IL-12; inflammatory bowel disease; monocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • CD40 Antigens / antagonists & inhibitors
  • Chemokine CXCL10 / antagonists & inhibitors
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology*
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / pathology
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / genetics
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / immunology
  • Immunity, Innate*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / cytology
  • Monocytes / immunology*
  • Primary Cell Culture
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology


  • Antibodies, Neutralizing
  • CD40 Antigens
  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Cxcr3 protein, mouse
  • Interleukin-23
  • Receptors, CXCR3
  • Interleukin-12
  • Interferon-gamma
  • I-kappa B Kinase
  • p38 Mitogen-Activated Protein Kinases