Human CD127 negative ILC2s show immunological memory

Laura Mathä; Lisette Krabbendam; Sergio Martinez Høyer; Balthasar A. Heesters; Korneliusz Golebski; Chantal Kradolfer; Maryam Ghaedi; Junjie Ma; Ralph Stadhouders; Claus Bachert; Lars Olaf Cardell; Nan Zhang; Gabriele Holtappels; Sietze Reitsma; Leanne Carijn Helgers; Teunis B.H. Geijtenbeek; Jonathan M. Coquet; Fumio Takei; Hergen Spits; Itziar Martinez-Gonzalez

doi:10.1084/jem.20231827

Human CD127 negative ILC2s show immunological memory

Laura Mathä, Lisette Krabbendam, Sergio Martinez Høyer, Balthasar A. Heesters, Korneliusz Golebski, Chantal Kradolfer, Maryam Ghaedi, Junjie Ma, Ralph Stadhouders, Claus Bachert, Lars Olaf Cardell, Nan Zhang, Gabriele Holtappels, Sietze Reitsma, Leanne Carijn Helgers, Teunis B.H. Geijtenbeek, Jonathan M. Coquet, Fumio Takei, Hergen Spits^*, Itziar Martinez-Gonzalez^*

^*Corresponding author for this work

Pulmonary Medicine

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

3 Downloads (Pure)

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.

Original language	English
Article number	e20231827
Journal	Journal of Experimental Medicine
Volume	221
Issue number	8
DOIs	https://doi.org/10.1084/jem.20231827
Publication status	Published - 18 Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 Mathä et al.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1084/jem.20231827Licence: CC BY

Human CD127 negative ILC2s show immunological memoryFinal published version, 6.24 MBLicence: CC BY

Cite this

Mathä, L., Krabbendam, L., Høyer, S. M., Heesters, B. A., Golebski, K., Kradolfer, C., Ghaedi, M., Ma, J., Stadhouders, R., Bachert, C., Cardell, L. O., Zhang, N., Holtappels, G., Reitsma, S., Helgers, L. C., Geijtenbeek, T. B. H., Coquet, J. M., Takei, F., Spits, H., & Martinez-Gonzalez, I. (2024). Human CD127 negative ILC2s show immunological memory. Journal of Experimental Medicine, 221(8), Article e20231827. https://doi.org/10.1084/jem.20231827

@article{c19980a2ee664045a76c4c8b2bd3afc5,

title = "Human CD127 negative ILC2s show immunological memory",

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.",

author = "Laura Math{\"a} and Lisette Krabbendam and H{\o}yer, {Sergio Martinez} and Heesters, {Balthasar A.} and Korneliusz Golebski and Chantal Kradolfer and Maryam Ghaedi and Junjie Ma and Ralph Stadhouders and Claus Bachert and Cardell, {Lars Olaf} and Nan Zhang and Gabriele Holtappels and Sietze Reitsma and Helgers, {Leanne Carijn} and Geijtenbeek, {Teunis B.H.} and Coquet, {Jonathan M.} and Fumio Takei and Hergen Spits and Itziar Martinez-Gonzalez",

note = "Publisher Copyright: {\textcopyright} 2024 Math{\"a} et al.",

year = "2024",

month = jun,

day = "18",

doi = "10.1084/jem.20231827",

language = "English",

volume = "221",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "8",

}

Mathä, L, Krabbendam, L, Høyer, SM, Heesters, BA, Golebski, K, Kradolfer, C, Ghaedi, M, Ma, J, Stadhouders, R, Bachert, C, Cardell, LO, Zhang, N, Holtappels, G, Reitsma, S, Helgers, LC, Geijtenbeek, TBH, Coquet, JM, Takei, F, Spits, H & Martinez-Gonzalez, I 2024, 'Human CD127 negative ILC2s show immunological memory', Journal of Experimental Medicine, vol. 221, no. 8, e20231827. https://doi.org/10.1084/jem.20231827

TY - JOUR

T1 - Human CD127 negative ILC2s show immunological memory

AU - Mathä, Laura

AU - Krabbendam, Lisette

AU - Høyer, Sergio Martinez

AU - Heesters, Balthasar A.

AU - Golebski, Korneliusz

AU - Kradolfer, Chantal

AU - Ghaedi, Maryam

AU - Ma, Junjie

AU - Stadhouders, Ralph

AU - Bachert, Claus

AU - Cardell, Lars Olaf

AU - Zhang, Nan

AU - Holtappels, Gabriele

AU - Reitsma, Sietze

AU - Helgers, Leanne Carijn

AU - Geijtenbeek, Teunis B.H.

AU - Coquet, Jonathan M.

AU - Takei, Fumio

AU - Spits, Hergen

AU - Martinez-Gonzalez, Itziar

PY - 2024/6/18

Y1 - 2024/6/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85202740528&partnerID=8YFLogxK

U2 - 10.1084/jem.20231827

DO - 10.1084/jem.20231827

M3 - Article

C2 - 38889332

AN - SCOPUS:85202740528

SN - 0022-1007

VL - 221

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 8

M1 - e20231827

ER -

Human CD127 negative ILC2s show immunological memory

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this