Allergic inflammation is exacerbated by allergen-induced type 2 innate lymphoid cells in a murine model of allergic rhinitis.

Abstract

Group 2 innate lymphoid cells (ILC2s) represent a new innate effector leukocyte population that mediates type-2 immune response. However, the contribution of ILC2s to allergic rhinitis (AR) is currently not well defined. To evaluate the potential existence and function of allergen-induced ILC2s in the experimental AR. We established a murine model of AR using ovalbumin (OVA) and aluminium hydroxide. The OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT). Then, we assessed ILC2s responses to mouse recombinant interleukin (rmIL)-25, anti-IL17RB antibody and CC chemokine ligand (CCL) 25 in the culture. After that, we adoptively transferred the NALT-derived ILC2s alone or plus rmIL-25 or anti-IL17RB antibody to the murine model of AR to investigate their role in the nasal allergic inflammation. We showed that ILC2s could be induced by OVA in the NALT of AR model. They were induced to secrete IL-5 and IL-13 by rmIL-25, and blocking of IL17RB contributed to the decreased production of these cytokines in the culture. We found that CCL25 induced the NALT-derived ILC2s migration through CC chemokine receptor 9 on ILC2s in vitro. Numbers of sneezing and nasal rubbing as well as counts of invasive eosinophils were all enhanced after the adoptive transfer of cultured ILC2s in vitro. The expressions of IL-5, IL-13, IL-25 and CCL25 in the NLF of allergic mice were also increased. These findings show that ILC2s play a proinflammatory role in the murine AR model, and also highlight ILC2s as a new target in the future AR therapy.