Project description:To compare transcriptomic profiles between skin and spleen iNKT cells, the analysis of global gene expressions in iNKT cells was performed using RNA-seq data obtained from iNKT cells purified from skin and spleen of CCR10+/EGFP mice.
Project description:We previously found that while CCR10+ ILCs are dominant in the healthy skin, they differentiate into CCR10- ILCs in the skin of mice with various dysregulated or inflammatory conditions, such as T/B cell-deficient Rag1-/- mice. These suggest that CCR10- ILCs are activated effector cells in response to altered skin environments. To gain clues about the functional mechanism and regulation of the ILC activation in the skin, we compared gene expression profiles of CCR10+ skin ILCs of wild-type (WT) mice versus CCR10- or CCR10low skin ILCs of WT and Rag1-/- mice using microarray analyses. Skin innate lymphoid cells were isolated by BD FACSAria sorting system. The microarry was perfomanced by Immunological Genome Project using Affymetrix arrays and used for analysis of gene expresssion of CCR10+ ILCs and CCR10- ILCs in different mice species as indicated.
Project description:We identified decreases in circulating CCR10+ Tregs in human hypertension. In order to better determine the phenotype of these cells, we performed bulk RNA sequencing of flow sorted human CCR10+ versus CCR10- Tregs from healthy control individuals. Results revealed evidence of increased T cell activation in CCR10+ Tregs.
Project description:Transcriptional profiling of mouse iNKT cells comparing wild type and Bcl11b deficient cell. The mice were treated with 4 μg of α-galactosylceramide. Goal was to determine the effects of transcription factor Bcl11b removal in iNKT cells. Intraperitoneal treatment with 4 μg of α-Galactosylceramide. Two pair of wild type (BCL11b F/F Vα14 transgenic) and Knock out (BCL11b F/F PLZF-Cre Vα14 transgenic)) mice were treated. Lymphocytes from spleen and liver were enriched and stain with PBS-57 Loaded CD1d tetramer. Pure iNKT cells were collected through cell sorter.
Project description:We confirm previous findings that adipose iNKT cells are transcriptionally distinct from canoncial splenic iNKT cells and we demonstrate that the adipose iNKT cell population is hetergeneous, containing two major functional subsets which can be segregated by expression of the surface marker NK1.1 (Klrb1c). Both of these adipose iNKT cell subsets play a role in the regulation of adipose tissue tissue homeostasis, including NK1.1+ iNKT cells, which produce IFNγ and induce adipose NK cell-mediated killing of adipose tissue macrophages.
Project description:Adipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs. We used microarrays to detail the global gene expression profiles that might underlie these phenotypic and functional differences in adipose iNKT cells compared to splenic iNKT cells.
Project description:We show that iNKT cells undergo rapid and extensive transcriptional remodeling after activation with the lipid antigen αGalactosylceramide (αGalCer). A common transcriptional framework underpins the activation of heterogeneous iNKT cell populations, including NKT1, NKT2 and NKT17 cells. We show that regulatory iNKT cell populations, including iNKT cells from epididymal adipose tissue, undergo blunted activation and show reduced transcriptional remodeling after αGalCer. We find that regulatory iNKT cell populations are enriched for memory-like KLRG1+ and cMAF+ iNKT subsets, and express gene signatures associated with adaptive Tr1 cells. IL-10 producing NKT10 cells express cMAF, and show enrichment for a cMAF-associated gene network. We also show that NKT10 cells are also phenotypically similar to adaptive Tr1 cells and NKTFH cells.
Project description:Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.