title: Novel role for surfactant protein A in gastrointestinal graft-versus-host disease.
abstract: Graft-versus-host disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal (GI) tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host Ags as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT. C57BL/6 (H2b; WT) and SP-A-deficient mice on a C57BL/6 background (H2b; SP-A(-/-)) mice underwent allogeneic or syngeneic BMT with cells from either C3HeB/FeJ (H2k; SP-A-deficient recipient mice that have undergone an allogeneic BMT [SP-A(-/-)alloBMT] or SP-A-sufficient recipient mice that have undergone an allogeneic BMT) or C57BL/6 (H2b; SP-A-deficient recipient mice that have undergone a syngeneic BMT or SP-A-sufficient recipient mice that have undergone a syngeneic BMT) mice. Five weeks post-BMT, mice were necropsied, and lung and GI tissue were analyzed. SP-A(-/-) alloBMT or SP-A-sufficient recipient mice that have undergone an allogeneic BMT had no significant differences in lung pathology; however, SP-A(-/-)alloBMT mice developed marked features of GI GVHD, including decreased body weight, increased tissue inflammation, and lymphocytic infiltration. SP-A(-/-)alloBMT mice also had increased colon expression of IL-1β, IL-6, TNF-α, and IFN-γ and as well as increased Th17 cells and diminished regulatory T cells. Our results demonstrate the first evidence, to our knowledge, of a critical role for SP-A in modulating GI GVHD. In these studies, we demonstrate that mice deficient in SP-A that have undergone an allogeneic BMT have a greater incidence of GI GVHD that is associated with increased Th17 cells and decreased regulatory T cells. The results of these studies demonstrate that SP-A protects against the development of GI GVHD and establishes a role for SP-A in regulating the immune response in the GI tract.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. kymberly.gowdy@nih.gov
authors.forename: Kymberly M
authors.initials: KM
authors.lastname: Gowdy
authors.forename: Diana M
authors.initials: DM
authors.lastname: Cardona
authors.forename: Julia L
authors.initials: JL
authors.lastname: Nugent
authors.forename: Charles
authors.initials: C
authors.lastname: Giamberardino
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Thomas
authors.forename: Sambuddho
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Sambudho
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Tereza
authors.initials: T
authors.lastname: Martinu
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Scott E
authors.initials: SE
authors.lastname: Plevy
authors.forename: Amy M
authors.initials: AM
authors.lastname: Pastva
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A