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(Journal of Leukocyte Biology. 2001;70:617-623.)
© 2001 by Society for Leukocyte Biology

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

Cristina Albanesi*, Claudia Scarponi*, Silvia Sebastiani*, Andrea Cavani*, Monica Federici*, Silvano Sozzani{dagger} and Giampiero Girolomoni*

* Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, IRCCS, Rome, Italy; and
{dagger} Laboratory of Inflammation and Signal Transduction, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy

Correspondence: Cristina Albanesi, Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta, 104, 00167 Rome, Italy. E-mail: c.albanesi{at}idi.it

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.

Key Words: Th2 • chemotaxis • interferon-{gamma} • TNF-{alpha}




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