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: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:The adenosine 2A receptor (A2AR) is expressed on regulatory T cells (Tregs), but the functional significance is currently unknown. We compared the gene expression between wild-type (WT) and A2AR knockout (KO) Tregs and between WT Tregs treated with vehicle or a selective A2AR agonist. FACS-sorted GFP positive Tregs from WT or A2AR KO FoxP3GFP mouse spleen and lymph nodes were incubated 18 hr with vehicle (DMSO), a separate set of WT Tregs were incubated with the selective A2AR agonist ATL1222 10 nM (Dogwood Pharmaceuticals, Inc.) for 18 hr prior to RNA isolation.
Project description:Donminant negative transform growth factor receptor II (DNR) mice were served as a murine primary biliary cirrhrosis model. CD4+Foxp3+ Regulatory T cells (Tregs) play a critical role in self-tolerance and in regulating PBC. In order to determine whether DNR mice derived Tregs processed defective function compared with WT Tregs, CD4+Foxp3+ Treg cells were sorted from DNR and WT mice, respectively, then gene expression analysis was performed by using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays CD4+Foxp3+ Tregs were sorted from the spleen of 10-week-old DNR mice and B6 wild-type mice, respectively. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DNR Tregs and WT Tregs in gene expression.
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.
Project description:We identified Pparg as a major orchestrator of the phenotype of adipose-tissue resident regulatory T cells (VAT Tregs). To establish the role of Pparg in shaping the VAT Tregs gene profile and cell dynamics, Tregs from lymph nodes and visceral adipose tissue of mice sufficient and deficient of Pparg expression in Tregs were double sorted for microarray analysis. All gene expression profiles were obtained from highly purified (double-sorted) T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled. Triplicates were generated for all groups. Raw data were preprocessed with the RMA algorithm in GenePattern and averaged expression values were used for analysis.