A cytokine-to-chemokine axis between T lymphocytes and keratinocytes can favor Th1 cell accumulation in chronic inflammatory skin diseases

J Leukoc Biol. 2001 Oct;70(4):617-23.

Abstract

The recruitment of T cells into the skin is regulated by chemokines released by resident cells. In this study, we found that normal human keratinocytes activated with Th1-derived supernatant (sup) expressed early (6-12 h) IP-10/CXCL10, MCP-1/CCL2, IL-8/CXCL8, and I-309/CCL1 mRNAs and with slower kinetics (24-96 h), RANTES/CCL5 and MDC/CCL22 mRNAs. Upon stimulation with the Th1 sup, keratinocytes secreted high levels of RANTES, IP-10, MCP-1, and IL-8 and moderate levels of I-309 and MDC. Although much less efficiently, Th2 sup could also induce keratinocyte expression of IL-8, IP-10, RANTES, and MCP-1 but not of I-309 and MDC. TARC/CCL17 was not significantly induced by any stimuli. Sup from keratinocytes activated with Th1-derived cytokines elicited a strong migratory response of Th1 cells and a limited migration of Th2 cells, whereas sup from Th2-activated keratinocytes promoted a moderate migration of Th1 and Th2 lymphocytes. Thus, keratinocytes appear considerably more sensitive to Th1- than to Th2-derived lymphokines in terms of chemokine release and can support the preferential accumulation of Th1 lymphocytes in the skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Cells, Cultured
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Chemotaxis, Leukocyte*
  • Chronic Disease
  • Clone Cells
  • Culture Media, Conditioned / pharmacology
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Dermatitis / immunology*
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / immunology
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / immunology
  • Keratinocytes / immunology*
  • RNA, Messenger / biosynthesis
  • Th1 Cells / immunology*
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Monoclonal
  • Chemokines
  • Culture Media, Conditioned
  • Cytokines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma