Differentiation and functional analysis of human TH17 cells

RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter

“…By binding to GATA-binding sites in the FOXP3 promoter, GATA-3 also negatively regulates FOXP3 expression and thereby inhibits Treg differentiation (20). The Th17-driving transcription factor RORC2 is expressed by both Treg and Th17 cells, whereas only Tregs express FOXP3 (21)(22)(23). In Tregs, FOXP3 suppresses transcriptional activity of RORC2 by direct interaction, thereby inhibiting Th17 differentiation (22,24).…”

“…Tregs were generated in the presence of TGF-b (5 ng/ml; R&D Systems, Minneapolis, MN) and neutralizing anti-IL-12 (5 mg/ml; R&D Systems) and anti-IFN-g (1 mg/ ml; R&D Systems) Abs. Th17 cells were differentiated as previously described (23) in the presence of TGF-b, IL-6 (20 ng/ml; PeproTech, Rocky Hill, NJ), b form of pro-IL-1 (IL-1b, 10 ng/ml; PeproTech), IL-23 (10 ng/ ml; eBioscience, San Diego, CA), and neutralizing anti-IL-12 and anti-IFN-g Abs. Dose titrations were performed and the optimal dose for each cytokine and Ab was determined in preliminary experiments.…”

Upstream Stimulating Factors Regulate the Expression of RORγT in Human Lymphocytes

“…Differentiation of naive CD4 + lymphocytes into Th17 cells is supported by the coordinated action of several cytokines, including IL-6, IL-23, and TGF-b (23). RORgT mRNA levels increase upon Th17 expansion in vitro, and increased RORgT mRNA levels in tissues positively correlate with Th17 activity observed in different inflammatory diseases (27)(28)(29). Mechanisms regulating the tissue-specific expression of RORgT are not well understood.…”

Impaired Oral Tolerance in ASD Children with Food Protein Induced Enterocolitis Syndrome (FPIES) – Altered Innate and Adaptive Immune Responses in ASD Children Recovered from FPIES in Comparison with non-ASD/FPIES and ASD/non-FPIES Children

“…These children did not reveal an increase in frequency of Th17 cells or IL-17 production. Since TGF-ß regulates (down-regulates) various immune responses and also serves as a key differentiation factor for regulatory T (Treg) cells, especially in the absence of inflammatory cytokines (Burgler et al, 2009;Zhou et al, 2009), it may be wondered whether ASD-IS children and in some-degree, ASD/FPIES children have impaired development or function of regulatory T cells. In the GI mucosa, IL-10 and TGF-ß producing Treg cells are believed to have a major role in the gut immune homeostasis (Lee and Mazmanian, 2010).…”