Innate Lymphoid Cells in Graft-Versus-Host Disease

Abstract

Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC—in many aspects—mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL‐22 producing RORγt+ ILC3 subset was recently found to be critical in the prevention of intestinal graft‐versus‐host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL‐22 producing ILC3 in improving allo‐HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD.

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance

“…Allogeneic donor‐derived T cells attacking host epithelial cells cause intestinal barrier loss, which is aggravated by radiotherapy and chemotherapy given in parallel to the transplantation. Subsequent translocation of intestinal bacteria leads to inflammation and activation of the donor immune system . Interestingly, ILC3 seem to play a protective role, since higher numbers of ILC3 in the circulation correlated with a lowered frequency of GvHD in AML patients .…”

Functional Reconstitution of Natural Killer Cells in Allogeneic Hematopoietic Stem Cell Transplantation

“…The lineage marker-negative innate lymphoid cells (ILCs) are a recently identified family of lymphoid cells that are preferentially located at barrier surfaces and can rapidly secrete immunoregulatory cytokines that correspond to the T H 1, T H 2, or T H 17/T H 22 immune response ( 97 , 98 ). Their role in allogeneic HSCT is gradually being elucidated and it has been recently shown that recipient-derived intestinal ILCs are important in mediating protection from gut GVHD ( 99 , 100 ). However, the nature and role of donor-derived ILC reconstitution remains largely unknown at present ( 101 ).…”

NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation

“…In this context, it is recently shown that gamma irradiation used in conditioning regimen before HSCT may exert a long-lasting effect on secondary lymphoid organ structure and function ( 40 ). Also, ILC2 appear to be involved in epithelial tissue repair, particularly in lung tissues; however, no data are available to support an actual protection exerted by these cells in GvHD-induced tissue damages ( 42 ).…”