title: Early-phase GVHD gene expression profile in target versus non-target tissues: kidney, a possible target?
abstract: GVHD is a major complication after allo-SCT. In GVHD, some tissues like liver, intestine and skin are infiltrated by donor T cells while others like muscle are not. The mechanism underlying targeted tropism of donor T cells is not fully understood. In the present study, we aim to explore differences in gene expression profile among target versus non-target tissues in a mouse model of GVHD based on chemotherapy conditioning. Expression levels of JAK-signal transducers and activators of transcription (STAT), CXCL1, ICAM1 and STAT3 were increased in the liver and remained unchanged (or decreased) in the muscle and kidney after conditioning. At the start of GVHD the expression levels of CXCL9, ITGb2, SAA3, MARCO, TLR and VCAM1 were significantly higher in the liver or kidney compared with the muscle of GVHD animals. Moreover, biological processes of inflammatory reactions, leukocyte migration, response to bacterium and chemotaxis followed the same pattern. Our data show that both chemotherapy and allogenicity exclusively induce expression of inflammatory genes in target tissues. Moreover, gene expression profile and histopathological findings in the kidney are similar to those observed in the liver of GVHD mice.
authors: Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. behnam.sadeghi@ki.se
authors: B
authors: B
authors: Sadeghi
authors: H
authors: H
authors: Al-Chaqmaqchi
authors: S
authors: S
authors: Al-Hashmi
authors: D
authors: D
authors: Brodin
authors: Z
authors: Z
authors: Hassan
authors: M
authors: M
authors: Abedi-Valugerdi
authors: A
authors: A
authors: Moshfegh
authors: M
authors: M
authors: Hassan
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology*; D053612:Janus Kinases / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050791:STAT Transcription Factors / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D059467:Transcriptome / Q000187:drug effects; D019172:Transplantation Conditioning; D014181:Transplantation Immunology
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases