IL-4 Enhances Keratinocyte Expression of CXCR3 Agonistic Chemokines

• Published in: The Journal of immunology (1950) 2000-08, Vol.165 (3), p.1395-1402
• Main Authors: Albanesi, Cristina, Scarponi, Claudia, Sebastiani, Silvia, Cavani, Andrea, Federici, Monica, De Pita, Ornella, Puddu, Pietro, Girolomoni, Giampiero
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; Adult; Calcium - metabolism; Calcium Signaling - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Line; Cell Movement - immunology; Cell-Free System - immunology; Chemokine CXCL10; Chemokine CXCL11; Chemokine CXCL9; Chemokines, CXC - biosynthesis; CXCR3 protein; Dermatitis, Allergic Contact - immunology; Dermatitis, Allergic Contact - metabolism; Dermatitis, Allergic Contact - pathology; g-Interferon; Humans; I-TAC protein; Intercellular Signaling Peptides and Proteins; Interferon-gamma - pharmacology; Interleukin-10 - physiology; Interleukin-17 - physiology; Interleukin-4 - physiology; IP-10 protein; Keratinocytes - immunology; Keratinocytes - metabolism; Mig protein; Nickel - immunology; Receptors, Chemokine - agonists; Receptors, Chemokine - biosynthesis; Receptors, CXCR3; Skin - immunology; Skin - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.3.1395

IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-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-gamma- or TNF-alpha-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-gamma 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-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.