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Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program.
London, Mariya; Bilate, Angelina M; Castro, Tiago B R; Sujino, Tomohisa; Mucida, Daniel.
Afiliação
  • London M; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Bilate AM; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Castro TBR; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Sujino T; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Mucida D; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA. mucida@rockefeller.edu.
Nat Immunol ; 22(4): 449-459, 2021 04.
Article em En | MEDLINE | ID: mdl-33686285
Mesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria and epithelium, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we uncovered the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (Treg) CD4+ T cells from mLN, lamina propria and intestinal epithelium segregate based on the gut layer they occupy; trajectory analysis suggests a stepwise loss of CD4 programming and acquisition of an intraepithelial profile. Treg cell fate mapping coupled with RNA sequencing and assay for transposase-accessible chromatin followed by sequencing revealed that the Treg cell program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of CD4-lineage-defining transcription factor ThPOK results in premature acquisition of an intraepithelial lymphocyte profile by mLN Treg cells, partially recapitulating epithelium imprinting. Thus, coordinated replacement of the circulating lymphocyte program with site-specific transcriptional and chromatin changes is necessary for tissue imprinting.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Diferenciação Celular / Linfócitos T Reguladores / Impressão Genômica / Montagem e Desmontagem da Cromatina / Linfócitos Intraepiteliais / Mucosa Intestinal / Linfonodos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Diferenciação Celular / Linfócitos T Reguladores / Impressão Genômica / Montagem e Desmontagem da Cromatina / Linfócitos Intraepiteliais / Mucosa Intestinal / Linfonodos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article