Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

Graft-versus-host-disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host antigens as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT

Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

BACKGROUND: Graft-versus-host-disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host antigens as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT. METHODS: C57BL/6 (H2b; WT) and SP-A deficient mice on C57BL/6 background (H2b; SP-A(−/−)) mice underwent allogeneic (Allo) or syngeneic (Syn) BMT with cells from either C3HeB/FeJ (H2k; SP-A(−/−)alloBMT or WTalloBMT) or C57Bl/6 (H2b; SP-A(−/−)synBMT or WTsynBMT) mice. 5 weeks post BMT, mice were necropsied and lung and gastrointestinal (GI) tissue were analyzed. RESULTS: SP-A(−/−)alloBMT or WTalloBMT 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 (Treg) cells. CONCLUSIONS: Our results demonstrate the first evidence 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 alloBMT have a greater incidence of GI GVHD that is associated with increased Th17 cells and decreased Tregs. 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