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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4749-4751. Prepublished online as a Blood First Edition Paper on March 1, 2005; DOI 10.1182/blood-2004-09-3622.
IMMUNOBIOLOGY Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potentialFrom DNAX Research Institute, Palo Alto, CA.
Interleukin-4 (IL-4), a major T-helper type 2 (Th2) cytokine, primes dendritic cells (DCs) for IL-12 production, suggesting a negative feedback loop to prevent dysregulated Th2 inflammation, such as allergy. We previously showed that human thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes of atopic dermatitis, activates CD11c+ DCs to induce the differentiation of naive CD4+ and CD8+ T cells into proallergic effectors. Here we show that TSLP primes DCs to produce large amounts of IL-12 after CD40 ligand stimulation, similar to IL-4 priming of DCs. In contrast to IL-4 priming, DCs activated with TSLP and CD40 ligand induce the differentiation of naive CD4+ T cells into effectors producing both Th1 and Th2 cytokines, a unique profile that is reminiscent of the late phase of allergy. Thus, TSLP is a major regulatory cytokine for IL-12 production by DCs, and TSLP-activated DCs could promote the persistence of Th2 inflammation even in the presence of IL-12-inducing signals. (Blood. 2005;105:4749-4751)
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