title: Altered T-cell entry and egress in the absence of Coronin 1A attenuates murine acute graft versus host disease.
abstract: Acute graft-versus-host disease (aGvHD) is a major limitation to the use of allogeneic stem cell transplantation for the treatment of patients with relapsed malignant disease. Previous work using animals lacking secondary lymphoid tissue (SLT) suggested that activation of donor T cells in SLT is critically important for the pathogenesis of aGvHD. However, these studies did not determine if impaired migration into, and more importantly, out of SLT, would ameliorate aGvHD. Here, we show that T cells from mice lacking Coronin 1A (Coro 1A(-/-)), an actin-associated protein shown to be important for thymocyte egress, do not mediate acute GvHD. The attenuation of aGvHD was associated with decreased expression of the critical trafficking proteins C-C chemokines receptor type 7 (CCR7) and sphingosine 1 phosphate receptor on donor T cells. This was mediated in part by impaired activation of the canonical NF-κB pathway in the absence of Coro 1A. As a result of these alterations, donor T cells from Coro 1A(-/-) mice were not able to initially traffic to SLT or exit SLT after BM transplantation. However, this alteration did not abrogate the graft-versus-leukemia response. Our data suggest that blocking T-cell migration into and out of SLT is a valid approach to prevent aGvHD.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: LeShara M
authors.initials: LM
authors.lastname: Fulton
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Taylor
authors.forename: James M
authors.initials: JM
authors.lastname: Coghill
authors.forename: Michelle L
authors.initials: ML
authors.lastname: West
authors.forename: Niko
authors.initials: N
authors.lastname: Föger
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
authors.forename: Albert S
authors.initials: AS
authors.lastname: Baldwin
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
mesh_terms: D000208:Acute Disease; D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000276:immunology* / Q000302:isolation & purification; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology; D000081025:Sphingosine-1-Phosphate Receptors; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: C515371:Ccr7 protein, mouse; D008840:Microfilament Proteins; D016328:NF-kappa B; D054400:Receptors, CCR7; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; C072061:coronin proteins
keywords: Coronin; Graft-versus-host disease; T cells; Transplantation
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