Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T H 2)-type allergic inflammation is not known.We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c + dendritic cells (DCs) and induced production of the T H 2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22).TSLP-activated DCs primed naïve T H cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-α, while downregulating IL-10 and interferon-γ. TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis.TSLP expression was associated with Langerhans cell migration and activation in situ.These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation. Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLPAbout 20% of the population in Western countries suffers from allergic diseases, which include asthma, allergic rhinitis, atopic dermatitis and food allergy 1 . Allergic inflammation is the result of a complex immunological cascade that leads to dysregulated production of T helper type 2 (TH2)-derived cytokines such as interleukin 4 (IL-4), IL-5 and IL-13 2-4 , which trigger immunoglobulin E (IgE) production, eosinophilia and mucus production [5][6][7] . Dendritic cells (DCs), which are professional antigen-presenting cells 8 , play an important role in the pathogenesis of allergic diseases 9-11 . However, the initial signal that primes DCs to induce T cells to produce proallergic TH2 cytokines is unknown. Epithelial cells are located at the sites of allergen entry into the body and interact closely with DCs in situ. However, it is not known whether DCs play a role in triggering the allergic immune cascade. Although skin keratinocytes and mucosal epithelial cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α) after activation 12 , none of these cytokines explain the mechanism that underlies the induction of allergic inflammation. Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, cloned from a murine thymic stromal cell line 13 . The TLSP receptor is a heterodimer that consists of the IL-7 receptor α chain (IL-7Rα) and a common γ-like receptor chain called TSLP receptor (TSLPR) [14][15][16][17] . Mouse TSLP supports murine early B and T cell developments 18,19 and does not appear to have any biological effects on murine DCs (unpublished data). In contrast, human TSLP activates CD11c + DCs, but does not appear to have any direct biological effects on B cells, T cells, NK cells, neutrophils or mast cells 17 . This is in accordance with the coexpression of IL-7Rα chain and TSLPR mRNA in CD11c + DCs, but not in other cell types. We show here that human TSLP potently activated ...

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.

Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.