Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation

Itziar M.G. et al., Immunity 45, 198–208 (2016)

Speaker: Chia-Ying Cheng (鄭嘉瑩)                            Time: 15:00~16:00, Sep. 14, 2016

Commentator: Prof. Jiu-Yao Wang (王志堯 醫師)     Place: Room 601

Abstract:

Group 2 innate lymphoid cells (ILC2s) have been described to produce abundant type-2 cytokines, including interleukin-5 (IL-5), IL-9 and IL-13, and contribute to allergic lung inflammation.  In allergic asthma, ILC2s are stimulated by cytokines including IL-33 released by damaged epithelium.  Although lung ILC2s have been shown to be critically involved in the initiation of allergic inflammation, the role of ILC2s in chronic allergy, which can result in recurrent lung diseases including asthma, remains to be elucidated.  The authors examined the fate of lung ILC2s uponallergen challenges in a mouse model of allergic inflammation in the lung to address the hypothesis that allergen-experienced ILC2s exhibit memory-like properties and enhanced allergic lung inflammation.  To investigate the role of allergen-experienced ILC2s in the immune response to inhaled allergen, the authors gave intranasal injections of IL-33, papain (PAP) or Aspergillus serine protease (ASP) into naive mice and analyzed lung ILC2s at different time points.  First, they found that some of the stimulated lung ILC2s lived for a long time, and a subset of activated ILC2s persisted in the mediastinal lymph node for several weeks after the initial activation.  Second, they found that allergen-experienced ILC2s were more responsive to an unrelated allergen than naïve ILC2s, and enhanced the papain-induced CD4⁺ T cell differentiation into Th2 cells. Third, IL-33-experienced ILC2s had a gene expression signature similar to that of memory T cells and were responsive to IL-25.  In conclusion, allergen-experienced ILC2s were more readily stimulated by allergen challenges, proliferation more vigorously and producing greater amounts of type 2 cytokines than naïve ILC2s.  This research highlights the potential mechanism that memory-like properties of allergen-experienced ILC2s may be responsible for the sensitization of individuals to multiple allergens.

References：

1.    Itziar M.G., Catherine A.S. et al. (2015). Lung ILC2s link innate and adaptive responses in allergic inflammation.  Trends Immunol. 36:189–195.

2.    Halim, T.Y., Steer, C.A. et al. (2014). Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40, 425–435.