Group 3 innate lymphoid cells in tissue damage and graft-versus-host disease pathogenesis

Innate lymphoid cells (ILC) have emerged as modulators of conditioning-induced tissue damage and development of graft-versus-host disease (GVHD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). This review highlights experimental and clinical evidence for a role of ILC in GVHD pathogenesis.

ILC are well known for their role in epithelial homeostasis and innate immunity. In addition, recent studies identified ILC as architects of intestinal responses to tissue damage after experimental radio and chemotherapy. Group 3 ILC, and their signature cytokine IL-22, can enhance intestinal stem cell regeneration and protect the stem cell niche from damage during experimental HSCT. Moreover, in leukemia patients undergoing HSCT conditioning, appearance of activated group 3 ILC prior to transplant is correlated to reduced incidence of acute GVHD.

ILC have a profound impact on the recovery from tissue damage and severity of GVHD in experimental models. Together with the available data from leukemia patients, this argues for in-depth analysis of the mechanisms of ILC function and the translation of experimental findings to clinical application. Ultimately, control of ILC activation, or of the cytokines they produce, could be employed to reduce GVHD lesion in patients receiving allogeneic HSCT.