Robert A Kastelein

..Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract...

..Thus, therapeutic targeting of IL-23 effectively inhibited multiple inflammatory pathways that are critical for driving CNS autoimmune inflammation...

..It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR...

..These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression...

..IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target...

..In this review, we aim to highlight the discoveries that have led to our current understanding of the biology of IL-23 and IL-27 in the context of their role in resistance to infection, immune-mediated inflammation, and cancer...

..These results show that IL-27 acts as a negative regulator of the developing IL-17A response in vivo, suggesting a potential therapeutic role for IL-27 in autoimmune diseases...

..Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity...

..Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4(+) T cells, it also directly acts on cells of the innate immune system...

..The implications of this shared usage of IL-1RAcP by IL-1(alpha and beta) and IL-33 are discussed...

..Using passive transfer studies, we confirm that these IL-23-dependent CD4(+) T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity...

..These findings, together with the altered IL-12/IL-23 balance induced by PGE2 in dendritic cells, further highlight the crucial role of the inflammatory microenvironment in Th17 cell development and regulation...

..This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases...

..We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours...

..Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells...

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..The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation...

..Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection...

..In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs...

..Consequently, IL-23 enables the persistence of the recognized tumor cells, accompanied by tumor-associated inflammation. This concept can explain tumor growth in the presence of large quantities of tumor-specific T cells...

..Our data identify CD161(+) CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation...

..By comparing the pathophysiological function of IL-12 and IL-23 in the context of host defense and autoimmune inflammation, we are beginning to understand the novel IL-23-IL-17 immune pathway...

..In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages...

..As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD)...

..2003; Villarino et al., 2003), indicate that they mediate complex and well-differentiated functions...

..We propose that IL-27 and IFN-alpha are important for early Th1 commitment and act upstream of IL-12 and IFN-gamma in this pathway...

..The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2...

..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...

..7 days, p < 0.01). Based on these results we propose that IL-23-induced changes of LC may be an important mechanism in directing the outcome of cutaneous immune responses...

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..Finally, IL-27, the latest addition to this family, is a heterodimer composed of the p40-related protein EBI3 (Epstein-Barr virus-induced gene 3) and the p35-related protein p28. IL-27 is involved in early Th1 initiation...

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..Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection...

..These results show that IL-23 complements the more dominant role of IL-12 in protection against a chronic fungal infection by an enhanced inflammatory cell response and distinct cytokine regulation...

..Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy...

..We propose that acquisition of, or alterations in, commensal bacteria influences intestinal immune homeostasis via direct regulation of the IL-25-IL-23-IL-17 axis...

..Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection...

..As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi...

..Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses...

..These data indicate that the B cell response to IL-27 is modulated during B cell differentiation and varies depending on the mode of B cell activation...

..These in vitro data describing a spirochete-induced release of IL-23 may help to define IL-17-dependent inflammatory responses in the disease...

..Interleukin (IL)-23 supports a distinct lineage of T cells producing IL-17 (Th17) that can mediate chronic inflammation. This study was performed to define the role of IL-23 and Th17 cells in chronic colitis in mice...