Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium

Abstract

It is well established that intraepithelial T lymphocytes (IELs) are derived from conventional single-positive (SP) thymocytes, as well as unconventional double-negative (DN) thymocytes and CD103+CD8αβ recent thymic emigrants (RTEs). We show that IELs can be divided into two groups according to their dependency on sphingosine 1-phosphate (S1P) for trafficking into the intestines. CD4 or CD8αβ naive lymphocytes originating from SP thymocytes express high levels of type 1 S1P receptor (S1P1), and their preferential migration into the large intestine is regulated by S1P. In contrast, RTEs migrate exclusively into the small intestine, whereas DN thymic IEL precursors expressing either TCRαβ or TCRγδ migrate into both the small and large intestines. S1P does not play a role in the migration pathways of these unconventional thymic IEL precursors. Thus, down-regulation of S1P1 expression or disruption of the S1P gradient halted conventional CD4 or CD8αβ IEL trafficking into the intestines, but did not affect the trafficking of unconventional thymic IEL precursors. These data are the first to demonstrate that a lipid-mediated system discriminates IELs originating from conventional and unconventional thymic precursors.

Lack of IL‐7 and IL‐15 signaling affects interferon‐γ production by, more than survival of, small intestinal intraepithelial memory CD8+ T cells

“…1 T cells may be detected in the SI-IEL, which express CD127/IL-7Ra at very low levels [57]. Here, we proved that despite the low frequency of CD127 1 SI-IEL cells, these few cells were capable of transducing signals from IL-7 in vitro, thus confirming the functionality of CD127/IL-7Ra on the gut CD8ab 1 T cells from the IEL (Fig.…”

Critical Role of Dendritic Cells in T Cell Retention in the Interfollicular Region of Peyer’s Patches

“…Flow cytometry and cell sorting were performed with FACSCanto II and FACSAria (BD Biosciences, San Diego, CA), respectively, as previously described (18). Briefly, cells were first preincubated with an anti-CD16/ CD32 mAb (2.4G2; BD Biosciences) and then stained with fluorescently labeled Abs specific for B220, CD3, CD4, CD8a, CD11b, CD11c, CD31, CD45, CD45RB, CD62L, CD69, or PD1 (all from BD Biosciences), or for FR4 (BioLegend, San Diego, CA).…”

“…Quantitative RT-PCR was performed with the LightCycler system (Roche Diagnostics, Basel, Switzerland) as reported previously (18). The primers and hybrid probes used for the RT-PCR were as follows: CCL19-specific oligonucleotide primers (sense, 59-GCCAAGAACAAA-GGCAACA-39, antisense, 59-CACACTCACATCGACTCTCTA-39), an FITC-labeled probe for CCL19 detection (59-TGGCCCAGGAAACCA-AGGACCA-39), and a LightCycler Red 640-labeled hybrid probe (59-AAGAGAGGACCAGGCCTCCT-39); CCL21-specific oligonucleotide primers (sense, 59-ACAGACACAGCCCTCAA-39, antisense, 59-CATGAG-GTGGCTGCTTT-39), an FITC-labeled probe for CCL21 detection (59-CCAGGAGATCCCCCACGAACTTC-39), and a LightCycler Red 640-labeled hybrid probe (59-AGCTGGGTGGTTCACGGT-39); GAPDH-specific oligonucleotide primers (sense, 59-TGAACGGGAAGCTCACTGG-39, antisense, 59-TCCACCACCCTGTTGCTGTA-39), an FITC-labeled probe for GAPDH detection (59-CTGAGGACCAGGTTGTCTCCTGCGA-39), and a LightCycler Red 640-labeled hybrid probe (59-TTCAACAGCAACT-CCCACTCTTCCACC-39) (Nihon Gene Research Laboratories, Sendai, Japan).…”

Vitamin B9 and ATP in the control and development of intestinal inflammation

“…function results in aberrant T-cell differentiation and cell trafficking in both systemic and intestinal compartments [24][25][26] .…”