ABSTRACT
Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increased in human cervical cancer (CxCa) tissues and tumour-infiltrating Treg cells (CD4+CD25hiCD127low), whereas blocking ERα with the antagonist ICI 182,780 abolishes FOXP3 expression and impairs the function of CxCa infiltrating Treg cells. Using a novel approach of co-immunoprecipitation with antibodies to E2 for capture, we identified binding of E2:ERα complexes to FOXP3 protein in CxCa-derived Treg cells. Chromatin immunoprecipitation analyses of male blood Treg cells revealed ERα occupancy at the FOXP3 promoter and conserved non-coding DNA elements 2 and 3. Accordingly, computational analyses of the enriched regions uncovered eight putative oestrogen response elements predicted to form a loop that can activate the FOXP3 promoter. Together, these data suggest that E2-mediated ERα signalling is critical for the sustenance of FOXP3 expression and Treg cell function in human CxCa via direct interaction of ERα with FOXP3 promoter. Overall, our work gives a molecular insight into ERα signalling and highlights a fundamental role of E2 in controlling human Treg cell physiology.
Subject(s)
Carcinoma, Squamous Cell/immunology , Estrogen Receptor alpha/metabolism , Forkhead Transcription Factors/metabolism , Promoter Regions, Genetic , Response Elements , T-Lymphocytes, Regulatory/immunology , Uterine Cervical Neoplasms/immunology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Estradiol/metabolism , Estrogen Receptor alpha/genetics , Estrogens/metabolism , Female , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Humans , Signal Transduction , Tumor Cells, Cultured , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathologyABSTRACT
The resistant starch (RS) contents of rice and waxy amaranth starch subjected to processing treatments like cooking by boiling, pressure cooking, roasting, extrusion cooking, frying and drum drying have been reported. Compared to the contents in the native starch, when expressed on dry wt basis, in both cases, cooking by boiling and pressure cooking resulted in increase in RS content whereas all other processing treatments resulted in a decrease in RS contents.
