RESUMO
Intraepithelial lymphocytes (IELs) are T cells important for the maintenance of barrier integrity in the intestine. Colon IELs are significantly reduced in both MyD88-deficient mice and those lacking an intact microbiota, suggesting that MyD88-mediated detection of bacterial products is important for the recruitment and/or retention of these cells. Here, using conditionally deficient MyD88 mice, we show that myeloid cells are the key mediators of TCRαß+ IEL recruitment to the colon. Upon exposure to luminal bacteria, myeloid cells produce sphingosine-1-phosphate (S1P) in a MyD88-dependent fashion. TCRαß+ IEL recruitment may be blocked using the S1P receptor antagonist FTY720, confirming the importance of S1P in the recruitment of TCRαß+ IELs to the colon epithelium. Finally, using the TNFΔARE/+ model of Crohn's-like bowel inflammation, we show that disruption of colon IEL recruitment through myeloid-specific MyD88 deficiency results in reduced pathology. Our results illustrate one mechanism for recruitment of a subset of IELs to the colon.
Assuntos
Colo , Mucosa Intestinal , Linfócitos Intraepiteliais , Lisofosfolipídeos , Camundongos Knockout , Células Mieloides , Fator 88 de Diferenciação Mieloide , Receptores de Antígenos de Linfócitos T alfa-beta , Esfingosina , Animais , Lisofosfolipídeos/metabolismo , Camundongos , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Colo/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Células Mieloides/imunologia , Células Mieloides/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Camundongos Endogâmicos C57BL , Cloridrato de Fingolimode/farmacologia , Doença de Crohn/imunologiaRESUMO
Interleukin-10 mediates regulatory functions of commensal-specific TH17 cells in murine small intestine.
