Chen, Chien‐Chang

Abstract CD8+ T cells represent a relatively under studied cell type in allergic lung inflammation, despite their presence in the mucosal tissues. This is because CD8+ T cells are normally associated with a Th1 response as opposed to Th2 or Th17 responses, as are the most cases with allergic inflammation. However, recent papers have shown the production of Th2 and Th17 cytokines in these cells, yet knowledge of their physiological role in allergic inflammation is incomplete. The presence of IL-17 in asthma patients contributes to a severe, steroid resistant phenotype. Therefore, determining contributors of IL-17 and their physiological role is paramount to understanding the disease. Our preliminary data which suggests memory Tc17 cells are generated in CD4-/- mice when sensitized intranasally to ovalbumin with IL-33. We believe Tc17 cells are responsible for the inflammation because the inflamed lung tissue contained elevated IL-17, and stimulated T cells from inflamed tissue produced elevated levels of IL-17 as well. Additionally, we were unable to induce inflammation in Rag-/- mice or TCRβ-/- mice, which pinpoints the cell responsible to CD8+ T cells in CD4-/- mice. Using these mice to study an exaggerated phenotype will allow us to more easily detect the contributions that happen to a lesser degree in wild type animals. This work create a more complete picture of the disease environment and lead to therapies which can account for the contribution of this cell type.

Abstract Group 2 innate lymphoid cells (ILC2s) reside in multiple organs in the body, where they play roles in immunity, tissue homeostasis, and metabolic regulation. However, little is known about the regulatory mechanisms of ILC2s in different organs. Here, we identified ILC2s in the mouse uterus and found that they express cell surface molecules, including the IL-33 receptor, ST2, that are roughly comparable to those expressed by lung ILC2s. Both in vivo and in vitro treatment with IL-33 induced type 2 cytokine production in uterine ILC2s, suggesting that they respond to IL-33 in a manner similar to ILC2s in other organs. Importantly, uterine ILC2s were nearly absent in ovariectomized mice and were increased in wild-type mice by estrogen administration, whereas lung ILC2s were unaffected by both ovariectomy and estrogen administration. Likewise, a marked reduction in uterine ILC2s was observed in mice deficient in estrogen receptor α or estrogen receptor β. Furthermore, uterine ILC2s highly expressed estrogen receptor α, and in vitro culture of isolated uterine ILC2s with 17β-estradiol modified expression of a number of genes. Finally, an increased prevalence in neonatal mortality was observed in litters from dams lacking the IL-33 receptor, ST2. Taken together, our findings indicate that unlike lung IL2Cs, uterine ILC2s are regulated by female sex hormones, which may specialize them for specific physiological functions.