ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation-mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127-CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127-CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.
Immunity, Innate , Immunologic Memory , Interleukin-7 Receptor alpha Subunit , Lymphocytes , Humans , Immunologic Memory/immunology , Animals , Interleukin-7 Receptor alpha Subunit/metabolism , Lymphocytes/immunology , Mice , Immunity, Innate/immunology , Leukocyte Common Antigens/metabolism , Cytokines/metabolism , Inflammation/immunology , Female , Mice, Inbred C57BL
