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

Publication ,  Journal Article
Laurie, SJ; Foster, JP; Bruce, DW; Bommiasamy, H; Kolupaev, OV; Yazdimamaghani, M; Pattenden, SG; Chao, NJ; Sarantopoulos, S; Parker, JS ...
Published in: Nat Commun
July 17, 2024

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 17, 2024

Volume

15

Issue

1

Start / End Page

6000

Location

England

Related Subject Headings

  • Transplantation, Homologous
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Lymphocytes
  • Intestine, Small
  • Immunity, Innate
  • Humans
  • Hematopoietic Stem Cell Transplantation
 

Citation

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MLA
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Laurie, S. J., Foster, J. P., Bruce, D. W., Bommiasamy, H., Kolupaev, O. V., Yazdimamaghani, M., … Serody, J. S. (2024). Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation. Nat Commun, 15(1), 6000. https://doi.org/10.1038/s41467-024-50263-7
Laurie, Sonia J., Joseph P. Foster, Danny W. Bruce, Hemamalini Bommiasamy, Oleg V. Kolupaev, Mostafa Yazdimamaghani, Samantha G. Pattenden, et al. “Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation.Nat Commun 15, no. 1 (July 17, 2024): 6000. https://doi.org/10.1038/s41467-024-50263-7.
Laurie SJ, Foster JP, Bruce DW, Bommiasamy H, Kolupaev OV, Yazdimamaghani M, et al. Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation. Nat Commun. 2024 Jul 17;15(1):6000.
Laurie, Sonia J., et al. “Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation.Nat Commun, vol. 15, no. 1, July 2024, p. 6000. Pubmed, doi:10.1038/s41467-024-50263-7.
Laurie SJ, Foster JP, Bruce DW, Bommiasamy H, Kolupaev OV, Yazdimamaghani M, Pattenden SG, Chao NJ, Sarantopoulos S, Parker JS, Davis IJ, Serody JS. Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation. Nat Commun. 2024 Jul 17;15(1):6000.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 17, 2024

Volume

15

Issue

1

Start / End Page

6000

Location

England

Related Subject Headings

  • Transplantation, Homologous
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Lymphocytes
  • Intestine, Small
  • Immunity, Innate
  • Humans
  • Hematopoietic Stem Cell Transplantation