Transcriptomics,Genomics

Dataset Information

152

Identification of a colitogenic memory CD4+ T cell population that mediates gastrointestinal GVHD


ABSTRACT: Using an experimental model of graft versus host disease (GVHD) to examine T cell-mediated inflammation within the colon, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin, CD11c, has a biased central memory phenotype and memory T cell transcriptional profile, possesses innate-like properties by gene expression analysis, and has increased expression of the gut-homing molecules, α4β7 and CCR9.  Using a number of complementary GVHD mouse models, we show that adoptive transfer of these cells results in TH1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality due to early accumulation of these cells in the GI tract.  The pathogenic effects of this CD4+ T cell population was critically dependent upon co-expression of the IL-23 receptor which was required for maximal inflammatory effects.  Colonic inflammation was regulated by IL-10 that was produced by non-Foxp3-expressing CD4+ T cells which attenuated lethality in the absence of functional CD4+ Foxp3+ T cells.  Thus, coordinate expression of CD11c and the IL-23R defines a novel IL-10 regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers as occurs in GVHD as well as other immune-mediated inflammatory bowel disorders. Overall design: Examination of the transcriptional profile of a novel population of CD4+ CD11c+ T cells that had a central memory T cell phenotype

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: William Drobyski 

PROVIDER: GSE83552 | GEO | 2016-08-12

SECONDARY ACCESSION(S): PRJNA326332

REPOSITORIES: GEO

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Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell-mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine G  ...[more]

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