IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines

Cristina Albanesi, Claudia Scarponi, Silvia Sebastiani, Andrea Cavani, Monica Federici, Ornella De Pità, Pietro Puddu, Giampiero Girolomoni

Research output: Contribution to journalArticlepeer-review

Abstract

IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-γ (Mig), and IFN-inducible T-cell α-chemoattractant (I-TAC) belong to the non- glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-γ or TNF-α-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel- specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN- γ and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-γ and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-γ alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-γ and TNF-α induction of IP- 10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.

Original languageEnglish
Pages (from-to)1395-1402
Number of pages8
JournalJournal of Immunology
Volume165
Issue number3
Publication statusPublished - Aug 1 2000

ASJC Scopus subject areas

  • Immunology

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