Disease relevance of Il25

• We have generated IL-25-deficient (il25(-/-)) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE) [1].
• The enforced expression of IL-25 in the lung itself failed to induce allergic airway inflammation, whereas the expression of IL-25 significantly enhanced antigen-induced T(H)2 cytokine production, eosinophil and CD4(+) T cell recruitment, and goblet cell hyperplasia in the airways [2].
• Conclusion IL-25 potently (single dose) induces sustained AHR and acute pulmonary inflammation with eosinophilia [3].
• Objective To determine the downstream factors employed by IL-25 to induce Th type-2 pulmonary inflammation and AHR [3].

High impact information on Il25

• We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17-producing T cells [1].
• Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity [1].
• Production of IL-25 by mast cells was also detected at protein levels by immunoblotting [4].
• Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling [5].
• METHODS: We examined the expression of IL-25 mRNA in the lungs of sensitized mice on antigen inhalation [2].

Biological context of Il25

• IL-25-induced AHR is dependent on the production of Th type-2 cytokines, and removal of IL-13 and its signal transduction pathway prevents IL-25-induced airways inflammation and AHR [3].
• IL-25 potently induces inflammatory cascades that may exacerbate allergic airways inflammation by promoting Th type-2 cytokine responses in conjunction with the up-regulation of factors (eotaxin and arg-I) that can amplify inflammation associated with allergic disorders [3].

Anatomical context of Il25

• Our results suggest a potential proremodeling effect of IL-17E on airway smooth muscle cells through the induction of ECM and that its receptor is upregulated by proinflammatory conditions [6].
• Here, we show that mast cells are also potent IL-25-producing cells [4].
• RESULTS: IL-25 mRNA was expressed in the lungs of sensitized mice on antigen inhalation, and the neutralization of IL-25 by soluble IL-25 receptor decreased antigen-induced eosinophil and CD4(+) T-cell recruitment into the airways [2].

Other interactions of Il25

• Increases in pro-proliferative cytokines, including tumor-necrosis superfamily 8, interleukin-17e, and hepatocyte growth factor, were found in nuclear-targeted Akt myocardial samples [7].

Analytical, diagnostic and therapeutic context of Il25

• Moreover, IL-25-induced enhancement of allergic airway inflammation was inhibited by the depletion of CD4(+) T cells or by the absence of signal transducer and activator of transcription 6 [2].

References