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

The recruitment of T cells into the skin is regulated by chemokines release d by resident cells. In this study, we found that normal human keratinocyte s 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 kin etics (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 I L-8 and moderate levels of I-309 and MDC. Although much less efficiently, T h2 sup could also induce keratinocyte expression of IL-8, IP-10, RANTES, an d 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 moder ate migration of Th1 and Th2 lymphocytes. Thus, keratinocytes appear consid erably more sensitive to Th1- than to Th2-derived lymphokines in terms of c hemokine release and can support the preferential accumulation of Th1 lymph ocytes in the skin.