Myeloid Cells and Sphingosine-1-Phosphate Are Required for TCRαβ Intraepithelial Lymphocyte Recruitment to the Colon Epithelium. J Immunol 2024 Jun 01;212(11):1843-1854
Date
04/03/2024Pubmed ID
38568091Pubmed Central ID
PMC11105980DOI
10.4049/jimmunol.2200556Scopus ID
2-s2.0-85193940128 (requires institutional sign-in at Scopus site)Abstract
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 TCRαβ+ IEL recruitment to the colon. Upon exposure to luminal bacteria, myeloid cells produce sphingosine-1-phosphate (S1P) in a MyD88-dependent fashion. TCRαβ+ IEL recruitment may be blocked using the S1P receptor antagonist FTY720, confirming the importance of S1P in the recruitment of TCRαβ+ 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.
Author List
Danielson SM, Lefferts AR, Norman E, Regner EH, Schulz HM, Sansone-Poe D, Orlicky DJ, Kuhn KAAuthor
Emilie Regner MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsColon
Crohn Disease
Fingolimod Hydrochloride
Intestinal Mucosa
Intraepithelial Lymphocytes
Lysophospholipids
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells
Myeloid Differentiation Factor 88
Receptors, Antigen, T-Cell, alpha-beta
Sphingosine
