Natural killer T (NKT) cells certainly are a specific subset of

Natural killer T (NKT) cells certainly are a specific subset of T lymphocytes that regulate immune system responses in the context of autoimmunity cancer and microbial infection. with the biggest NKT cell populations localizing towards the liver organ lungs spleen and bone tissue marrow. Flumazenil That is regarded as mediated by differences in chemokine receptor expression profiles. However the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection. however CXCR6?/? and CXCR6?/+ mice exhibited a similar frequency of apoptotic CD1d-reactive cells in liver sections and freshly isolated liver lymphocytes (90). We found no difference in the apoptosis rates of cultured NKT cells purified from the livers of CXCR6+/+ and CXCR6?/? mice (91) but observed an accumulation of NKT cells in the bone marrow suggesting an alteration in homing. Interestingly mice deficient in Id2 exhibit impaired survival of liver NKT cells which is associated with reduced expression of CXCR6 and the survival factors Bcl-2 and Bcl-XL (79). Similarly hepatic NKT cells from CXCR6-deficient mice expressed lower levels of Bcl-2 suggesting a role in survival (79). Despite the conflicting reports it seems likely that CXCR6 plays a role in regulating survival of NKT cells within certain tissue environments [since NKT cell numbers are normal in most tissues (90-92)] or under specific culture conditions. A separate study found that NKT cells in CC chemokine receptor 5 (CCR5)-deficient mice were resistant to activation-induced apoptosis and created more IL-4 leading to enhanced liver organ injury inside a style of ConA-induced hepatitis (93). Oddly enough despite an impairment of activation-induced cell loss of life there have been no problems in Fas-mediated apoptosis in these NKT cells. In human being T cells CCR5-reliant apoptosis continues to be reported in response to high concentrations from the chemokine ligand CCL5 (94) or ligation of CCR5 from the human being immunodeficiency disease (HIV) envelope protein gp160 (95). In such cases however there is improved susceptibility to caspase-8-reliant cell loss of life through induction of FasL (95). These research point to a job for chemokine receptors in influencing lymphocyte success and increase an evergrowing body of books demonstrating the power of chemokine receptors to modify several cellular functions furthermore with their traditional tasks in regulating leukocyte recruitment and placing. Organic killer T cell homeostasis is definitely controlled from the microbiome. Germ-free Swiss-Webster and C57BL/6 mice show variable modifications in thymic spleen and liver organ NKT cell populations in comparison to conventionally housed pets (96-98). This variability may reveal differences in Flumazenil the traditional microbiota in charge mice housed in various facilities (98). Nevertheless germ-free mice regularly exhibited increased amounts of NKT cells in the intestinal lamina propria and lungs (96 98 NKT cell build up appears to derive from dysregulated CXCL16 manifestation and could become reversed by CXCL16 blockade or neonatal contact with regular microbiota (96). Bacterias from the genera comprise >50% from the bacterias in the human being gut (99) and offers been shown Flumazenil to generate α-GalCer derivatives capable of regulating NKT cells (100 101 One such compound α-GalCerBf binds to CD1d and activates NKT Flumazenil cells and Hbb-bh1 led to variable expansion of NKT cells (100). also generates GSL-Bf717 an α-GalCer analog that inhibits NKT cell activity and restored NKT cell homeostasis in germ-free mice (101). Therefore it appears that the composition of the intestinal microbiota influences the homeostasis of NKT cells within the colon and lungs and may also exert influences on NKT cells within other tissues. Adding further complexity NKT cells also influence bacterial colonization in the intestine (102) and engagement of epithelial CD1d contributes to intestinal epithelial cell-dependent regulation of mucosal homeostasis via IL-10 production (103) highlighting the intricate interactions which take place between host cells and the microbiota. NKT Cell Tissue Localization Patterns In mice NKT cells are first detected in the thymus at day 5-6 after birth and in the periphery after day 8 (12 104 They.