title: Role of IL-26+CD26+CD4 T Cells in Pulmonary Chronic Graft-Versus-Host Disease and Treatment with Caveolin-1-Ig Fc Conjugate.
abstract: Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells. Moreover, we showed that IL-26 increased collagen synthesis in fibroblasts in vitro and that collagen contents were increased in a murine GVHD model using IL26 transgenic mice. In vitro analysis demonstrated a significant increase in IL-26 production by CD4 T cells following CD26 costimulation, while immunoglobulin Fc domain fused with the N-terminal of caveolin-1, the ligand for CD26, (Cav-Ig) effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of clinical and histologic features of GVHD without interrupting engraftment of donor-derived human cells, with preservation of the graft-versus-leukemia effect. We concluded that cGVHD of the lungs is caused in part by IL-26+CD26+CD4 T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy.
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Hematology, Juntendo University Shizuoka Hospital, Nagaoka 1129, Izunokuni-city, Shizuoka 410-2295, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwao
authors.affiliation: Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road- Box 100278, Room MSB M410A, Gainesville, FL 32610, U.S.A.
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D051242:Caveolin 1 / Q000627:therapeutic use*; D002908:Chronic Disease; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
chemical_list: D051242:Caveolin 1; C406767:IL26 protein, human; D007378:Interleukins; D011993:Recombinant Fusion Proteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4