Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation

Sonia J. Laurie, Joseph P. Foster, Danny W. Bruce, Hemamalini Bommiasamy, Oleg V. Kolupaev, Mostafa Yazdimamaghani, Samantha G. Pattenden, Nelson J. Chao, Stefanie Sarantopoulos, Joel S. Parker, Ian J. Davis and Jonathan S. Serody ()
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Sonia J. Laurie: University of North Carolina School of Medicine
Joseph P. Foster: University of North Carolina School of Medicine
Danny W. Bruce: University of North Carolina School of Medicine
Hemamalini Bommiasamy: University of North Carolina School of Medicine
Oleg V. Kolupaev: University of North Carolina School of Medicine
Mostafa Yazdimamaghani: University of North Carolina School of Medicine
Samantha G. Pattenden: University of North Carolina Eshelman School of Pharmacy
Nelson J. Chao: Duke Cancer Institute
Stefanie Sarantopoulos: Duke Cancer Institute
Joel S. Parker: University of North Carolina School of Medicine
Ian J. Davis: University of North Carolina School of Medicine
Jonathan S. Serody: University of North Carolina School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50263-7

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