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Human ectoenzyme-expressing ILC3: immunosuppressive innate cells that are depleted in graft-versus-host disease
- Source :
- Blood advances, 3(22), 3650-3660. American Society of Hematology
- Publication Year :
- 2019
-
Abstract
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often associated with chemotherapy- and radiotherapy-induced host tissue damage, leading to graft-versus-host disease (GVHD). Innate lymphoid cells (ILC) have an essential role in tissue homeostasis and tissue repair via their production of interleukin (IL)-22, which acts on intestinal stem cells. The tissue healing capacities of ILC via IL-22 in the context of allo-HSCT and GVHD has previously been demonstrated in a mouse model for acute GVHD. We investigated potential other ways of ILC-mediated tissue protection against GVHD. Tissue injury leads to the release of danger-associated molecular patterns (DAMPs). DAMPs interact with purinergic receptors and ectoenzymes on immune cells and induce pleiotropic effects, including activation of proinflammatory antigen-presenting cells and immunosuppressive effects via the generation of adenosine. Here, we report a novel subset of human ILC3 that coexpress the ectoenzymes CD39 and CD73 (ecto(+) ILC3). Ecto(+) ILC3 express RORγt and were present in the oral-gastrointestinal tract and bone marrow. ILC3 ectoenzyme expression is modulated by the proinflammatory cytokine IL-1β. Extracellular adenosine triphosphate (eATP) stimulated ecto(+) ILC3 to produce IL-22 and adenosine. Activated ecto(+) ILC3 suppressed autologous T-cell proliferation in coculture experiments via the production of adenosine. In allo-HSCT recipients, intestinal GVHD was associated with reduced proportions of ecto(+) ILC3 and decreased levels of adenosine and its metabolite inosine. Taken together, ecto(+) ILC3 have immunosuppressive properties, but in patients with GVHD, ecto(+) ILC3 are depleted. A lack of ecto(+) ILC3 and subsequent reduced capacity to neutralize DAMPs may contribute to the development of GVHD.
- Subjects :
- Adult
Male
Graft vs Host Disease
Gene Expression Regulation, Enzymologic
Proinflammatory cytokine
Ectopic Gene Expression
Immunophenotyping
Interleukin 22
Immune system
Adenosine Triphosphate
medicine
Immune Tolerance
Humans
Transplantation, Homologous
Lymphocytes
Tissue homeostasis
Aged
Cell Proliferation
Adenosine Triphosphatases
Transplantation
Chemistry
Hydrolysis
Innate lymphoid cell
fungi
Hematopoietic Stem Cell Transplantation
Hematology
Middle Aged
medicine.disease
Adenosine
Immunity, Innate
Graft-versus-host disease
surgical procedures, operative
Cancer research
Cytokines
Female
Stem cell
Biomarkers
medicine.drug
Subjects
Details
- ISSN :
- 24739537 and 24739529
- Volume :
- 3
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Blood advances
- Accession number :
- edsair.doi.dedup.....162e634dce3f3d566d982eca50835348