Interleukin-33-Activated Dendritic Cells Induce the Production of Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine

Abstract

Background: Interleukin (IL)-33, a new member of the IL-1 cytokine family, is involved in T helper (Th)2-type responses in a wide range of diseases and is mediated by expression of the ST2 receptor in many immune cells. As the effects of IL-33 on dendritic cells (DCs) remain controversial, we investigated the ability of IL-33 to modulate the functions of these cells. Methods: DCs were derived from mouse bone marrow, and the expression of the IL-33 receptor ST2 was examined by fluorescence-activated cell sorting and RT-PCR. The responses of the DCs to IL-33 were examined by RT-PCR and ELISA, and activation of mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Results: ST2 ligand mRNA and protein were detectable in DCs. IL-33 induced the production of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 and the activation of extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase and p38 MAPK. Conclusions: DCs respond directly to IL-33 through ST2. The interaction between IL-33 and DCs may represent a new pathway to initiate Th2-type immune responses. IL-33 and ST2 may play important roles in allergic inflammation.

Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte‐derived Langerhans cells in patients with atopic dermatitis

“…With regard to DC, phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase and p38 MAPK are activated under the stimulation of IL-33, and the production of both CCL17 and CCL22 is promoted by murine DC. 20 Thus, these data show that p38 MAPK signaling influences the regulation of chemokine production by the immune cells. Our findings demonstrate that a H4R antagonist inhibited the phosphorylation of p38 MAPK in the MoLC to reduce their chemokine production.…”

“…p38 MAPK regulates nuclear factor‐κB activation to produce CCL17. With regard to DC, phosphorylation of extracellular signal‐regulated kinase 1/2, c‐Jun N‐terminal kinase and p38 MAPK are activated under the stimulation of IL‐33, and the production of both CCL17 and CCL22 is promoted by murine DC . Thus, these data show that p38 MAPK signaling influences the regulation of chemokine production by the immune cells.…”

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

“…NH-2 terminus has NLS motif and the full length IL-33 localizes to nucleus and regulates transcriptional activity (26). Proteolysis allows extracellular presence of IL-33 and stimulates IL1RL1 receptors on Th-2 cells (27). It may function as an ‘alarmin’ in directing immune/inflammatory response to the sites of tissue damage, similar to IL-1α and HMGB1 (28).…”

Role of IL-33 and Its Receptor in T Cell-Mediated Autoimmune Diseases

“…DCs respond directly to IL-33 through ST2 [44]. DCs not only respond to IL-33 but also produce IL-33 in allergic condition [45].…”