Abstract
Type II innate lymphoid cells (ILC2s) maintain homeostasis and barrier integrity in mucosal tissues. In both mice and humans, ILC2s poorly reconstitute after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Determining the mechanisms involved in their impaired reconstitution could improve transplant outcomes. By integrating single-cell chromatin and transcriptomic analyses of transplanted ILC2s, we identify a previously unreported population of converted ILC1-like cells in the mouse small intestine post-transplant. Exposure of ILC2s to proinflammatory cytokines resulted in a mixed ILC1-ILC2 phenotype but was able to convert only a small population of ILC2s to ILC1s, which were found post-transplant. Whereas ILC2s protected against acute graft-versus-host disease (aGVHD) mediated mortality, infusion of proinflammatory cytokine-exposed ILC2s accelerated aGvHD. Interestingly, murine ILC2 reconstitution post-HSCT is decreased in the presence of alloreactive T cells. Finally, peripheral blood cells from human patients with aGvHD have an altered ILC2-associated chromatin landscape compared to transplanted controls. These data demonstrate that following transplantation ILC2s convert to a pro-pathogenic population with an ILC1-like chromatin state and provide insights into the contribution of ILC plasticity to the impaired reconstitution of ILC2 cells, which is one of several potential mechanisms for the poor reconstitution of these important cells after allo-HSCT.
Recommended Citation
S. J. Laurie and J. P. Foster and D. W. Bruce and H. Bommiasamy and O. V. Kolupaev and M. Yazdimamaghani and S. G. Pattenden and N. J. Chao and S. Sarantopoulos and J. S. Parker and I. J. Davis and J. S. Serody, "Type II Innate Lymphoid Cell Plasticity Contributes To Impaired Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation," Nature Communications, vol. 15, no. 1, article no. 6000, Nature Research, Dec 2024.
The definitive version is available at https://doi.org/10.1038/s41467-024-50263-7
Department(s)
Chemical and Biochemical Engineering
Publication Status
Open Access
International Standard Serial Number (ISSN)
2041-1723
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Dec 2024
PubMed ID
39019846
Comments
University of North Carolina, Grant P30-ES010126