The formation of memory-like innate lymphoid cells 2 in allergic asthma

Abstract

Abstract Numerous studies have been suggested that ILC2s play a critical role in the initiation of allergic asthmatic airway inflammation, but their property and role in chronic allergic lung inflammation has not been well established. Our study found that purified allergen-experienced ILC2s produce more cytokines than naive ILC2s when stimulated by suboptimal amounts of IL-33 and IL-2 in vitro. Furthermore, upon allergen intranasal re-challenge, allergen-experienced ILC2s proliferate more vigorously and produce much greater amounts of type 2 cytokines than naive ILC2s. These results suggested that allergen-experienced ILC2s showed some memory-like properties in allergic asthma. To further characterize these memory-like ILC2s, we analyzed the expression of some activation surface markers, such as KLRG1, CD62L, CD69, ST2, ICOS, NKG2D, CD44, CD25 and CD122 on ILC2s in the lungs of naive and IL-33-treated mice at different time point. The results showed that during the initial expansion phase, IL-33 treatment resulted in a rapid increase in the number of CD25− ILC2s cells, which peaked at d6. And then the CD25− ILC2 population in the lung started to contract, the number of CD25− ILC2s cells was rapidly declined at d14, a time point that the numbers of CD25+ ILC2s reached their peak. Both of CD25− and CD25+ ILC2s rapidly declined at d30, however, the numbers of CD25+ ILC2s was much higher than CD25− ILC2. Thus, these results suggested that allergen-experienced ILC2s could differentiate into two different memory potential ILC2 subsets, namely CD25− short-term surviving effector ILC2s cells an CD25+ long-term surviving memory ILC2s cells. This work was supported by grants (2015CB943203, 31300730, 81272315, 2016GCC09)