Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential.
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.
Watanabe
Norihiko
N
DNAX Research Institute, Palo Alto, CA, USA.
Hanabuchi
Shino
S
Marloie-Provost
Marie-Annick
MA
Antonenko
Svetlana
S
Liu
Yong-Jun
YJ
Soumelis
Vassili
V
D039521:CD11c Antigen / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis / Q000378:metabolism*; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D022423:Myeloid Cells / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology*; D013997:Time Factors; D000094632:Thymic Stromal Lymphopoietin
D039521:CD11c Antigen; D015704:CD4 Antigens; D019013:CD40 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin