title: Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used to treat hematopoietic cell disorders but is often complicated by graft-versus-host disease (GVHD), which causes severe epithelial damage. Here we have investigated longitudinally the effects of induction chemotherapy, conditioning radiochemotherapy, and allogeneic HSCT on composition, phenotype, and recovery of circulating innate lymphoid cells (ILCs) in 51 acute leukemia patients. We found that reconstitution of ILC1, ILC2, and NCR(-)ILC3 was slow compared with that of neutrophils and monocytes. NCR(+) ILC3 cells, which are not present in the circulation of healthy persons, appeared both after induction chemotherapy and after allogeneic HSCT. Circulating patient ILCs before transplantation, as well as donor ILCs after transplantation, expressed activation (CD69), proliferation (Ki-67), and tissue homing markers for gut (α4β7, CCR6) and skin (CCR10 and CLA). The proportion of ILCs expressing these markers was associated with a decreased susceptibility to therapy-induced mucositis and acute GVHD. Taken together, these data suggest that ILC recovery and treatment-related tissue damage are interrelated and affect the development of GVHD.
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: J Marius
authors.initials: JM
authors.lastname: Munneke
authors.affiliation: Center for Infectious Medicine, Department of Medicine and.
authors.forename: Andreas T
authors.initials: AT
authors.lastname: Björklund
authors.affiliation: Center for Infectious Medicine, Department of Medicine and.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Mjösberg
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;
authors.forename: Karin
authors.initials: K
authors.lastname: Garming-Legert
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Jochem H
authors.initials: JH
authors.lastname: Bernink
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huisman
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.affiliation: Center for Infectious Medicine, Department of Medicine and Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007113:Immunity, Innate; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D052016:Mucositis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D019394:Ki-67 Antigen