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Chitin, a polysaccharide found in the fungal cell wall and the exoskeletons of house dust mites and cockroaches, has garnered attention as a potential immunoreactive allergen. Mammals have evolved to express chitin-degrading chitinases (acidic mammalian chitinase/AMCase and chitotriosidase) that may modulate immune responses to chitin. We have previously reported that mice deficient in AMCase ( Chia -/-) demonstrated better lung function during allergic fungal asthma. As expected, we show that mice overexpressing AMCase (SPAM mice) had worse airway hyperreactivity (AHR) during allergic fungal asthma. We further demonstrate that chitin-positive Aspergillus fumigatus conidia are detectable in the allergic lung during chronic exposure. Lung function in Chia -/- and SPAM mice directly correlated with the level of chitinase activity during chronic fungal exposure ( Chia -/- mice, negligible chitinase activity, lower AHR; SPAM mice, heightened chitinase activity, higher AHR), suggesting that the breakdown of chitin promoted AHR. However, chronic exposure of normal mice to purified A. fumigatus chitin resulted in only moderate inflammatory changes in the lung which were not sufficient to induce AHR. Moreover, despite having dramatic differences in chitinase activity, chronic exposure of Chia -/- and SPAM mice to purified A. fumigatus chitin likewise did not modulate AHR. Collectively, these results indicate that chronic exposure to fungal chitin alone is incapable of driving AHR. Furthermore, our data suggests that the chitinase-mediated degradation of chitin associated with A. fumigatus conidia may facilitate unmasking and/or liberation of other fungal cell wall components that drive inflammatory responses which contribute to AHR.

Background: The role of Th17 cells in prostate cancer (PCa) is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells., Methods: In this study, we aimed to characterize the role of Batf-dependent Th17 cells in PCa by crossbreeding Batf knockout (Batf-/-) mice with mice conditionally mutant for Pten. We found that Batf-/- mice had changes in the morphology of prostate epithelial cells compared to normal mice, and Batf-/- mice deficient in Pten (named Batf-) had smaller prostate size and developed fewer invasive prostate adenocarcinomas than Pten-deficient mice with Batf expression (named Batf+). The prostate tumors in Batf- mice showed reduced proliferation, increased apoptosis, decreased angiogenesis and inflammatory cell infiltration, and activation of NF-κB signaling. Moreover, Batf- mice showed significantly reduced IL-23/IL-23R signaling. In the prostate stroma of Batf- mice, IL-23R-positive cells were decreased considerably compared to Batf+ mice. Splenocytes and prostate tissues from Batf- mice cultured under Th17 differentiation conditions expressed reduced IL-23/IL-23R than cultured cells from Batf+ mice. Anti-IL23p19 antibody treatment of Pten-deficient mice reduced prostate tumors and angiogenesis compared to control IgG-treated mice. In human prostate tumors, BATF mRNA level was positively correlated with IL23A and IL-23R but not RORC., Conclusion: Our novel findings underscore the crucial role of IL-23/IL23R signaling in mediating the function of Batf-dependent Th17 cells, thereby promoting PCa initiation and progression. This highlights the Batf-IL-23R axis as a promising target for the development of innovative strategies for PCa prevention and treatment., (© The Author(s) 2024. Published by Oxford University Press.)