Human CD127 negative ILC2s show immunological memory
Laura Mathä, Lisette Krabbendam, S. Høyer, Balthasar A. Heesters, Korneliusz Golebski, Chantal M. A. Kradolfer, Maryam Ghaedi, Junjie Ma, Ralph Stadhouders, Claus Bachert, Lars‐Olaf Cardell, Nan Zhang, Gabriële Holtappels, Sietze Reitsma, Leanne C. Helgers, Teunis B. H. Geijtenbeek, Jonathan M. Coquet, Fumio Takei, Hergen Spits, Itziar Martínez-González
Abstract
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.