Osteopontin and iCD8α Cells Promote Intestinal Intraepithelial Lymphocyte Homeostasis

Abstract

Intestinal intraepithelial lymphocytes (IEL) comprise a diverse population of cells residing in the epithelium at the interface between the intestinal lumen and the sterile environment of the lamina propria. Because of this anatomical location, IEL are considered critical components of intestinal immune responses. Indeed, IEL are involved in many different immunological processes ranging from pathogen control to tissue stability. However, despite their critical importance in mucosal immune responses, very little is known about the homeostasis of different IEL subpopulations. The phosphoprotein osteopontin is important for critical physiological processes, including cellular immune responses such as survival of Th17 cells and homeostasis of NK cells, among others. Because of its impact in the immune system, we investigated the role of osteopontin in the homeostasis of IEL. Here, we report that mice deficient in the expression of osteopontin exhibit reduced numbers of the IEL subpopulations TCRγδ + , TCRβ + CD4 + , TCRβ + CD4 + CD8α + and TCRβ + CD8αα + cells in comparison to wild-type mice. For some IEL subpopulations the decrease in cells numbers could be attributed to apoptosis and reduced cell division. Moreover, we show in vitro that exogenous osteopontin stimulates the survival of murine IEL subpopulations and unfractionated IEL derived from human intestines, an effect mediated by CD44, a known osteopontin receptor. We also show that iCD8α IEL, but not TCRγδ + IEL, TCRβ + IEL or intestinal epithelial cells, can promote survival of different IEL populations via osteopontin, indicating an important role for iCD8α cells in the homeostasis of IEL.

Oxidized phospholipids cause changes in jejunum mucus that induce dysbiosis and systemic inflammation

“…4 B). Osteopontin has been shown to be important for intestinal intraepithelial lymphocyte regulation of the microbiota in mice ( 70 , 71 ).…”

Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis

“…A: The results are shown for 17 genes whose expression was previously reported to have decreased in the jejunum of Ldlr −/− mice fed a WD ( 22 ): intestinal alkaline phosphatase ( Alp1 ) ( 34 , 35 , 36 , 37 , 38 , 39 ); apolipoprotein A-I ( ApoA -I) ( 40 , 41 ); atonal homolog 1 ( Atoh1 ) ( 27 , 28 , 29 ); defensin 4 ( Defb4 ) ( 42 , 43 ); delta-like canonical notch ligand 4 ( Dll4 ) ( 44 ); growth factor independent protein 1 ( Gfi1 ) ( 30 ); interleukin 22 ( Il22 ) ( 31 , 45 ); interleukin 23 ( Il23 ) ( 31 , 46 , 47 ); interleukin 36γ ( Il36γ ) ( 31 ); lysozyme ( Lyz ) ( 48 ); mucin 2 ( Muc2 ) ( 49 ); notch receptor 1 ( Notch1 ) ( 33 ); notch receptor 2 ( Notch2 ) ( 31 ); regenerating islet-derived 3b ( Reg3b ) ( 50 ); regenerating islet-derived 3g ( Reg3g ) ( 51 ); surfactant A ( Sftpa1 ) ( 52 ); and defensin 3 ( Defb3 ) ( 53 , 54 ). B: The results are shown for two genes whose expression was previously reported to have increased in the jejunum of Ldlr −/− mice fed a WD ( 22 ): LPS-binding protein ( Lbp ) ( 55 , 56 ); secreted phosphoprotein 1 ( Spp1 ) ( 57 , 58 ). Statistical analysis of the data in Fig.…”

Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis

“…Dysregulation of IEL subpopulations contributes to mucosal inflammation. To determine the role of CA on IEL during DSS colitis, we isolated IEL from the colon and performed flow cytometry to evaluate IEL subpopulations ( Figure 5A shows the gating strategy) ( 27 ). CA-treated DSS mice showed significantly higher number of TCRγδ + ( Figure 5B ), TCRγδ + CD8αα + ( Figure 5E ), TCRβ + CD8αβ + ( Figure 5F ), and TCRγδ − TCRβ − CD8αα + ( Figure 5G ) IEL in comparison with their DSS counterparts.…”