PMID- 31882422 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20200622 IS - 1550-8080 (Electronic) IS - 0091-7370 (Linking) VI - 49 IP - 6 DP - 2019 Nov TI - NFATc1 is a Necessary Transcription Factor in Polarisation of T Helper Type 2 Lymphocytes Induced by Thymic Stromal Lymphopoietin. PG - 722-729 AB - Thymic stromal lymphopoietin (TSLP) activates lung dendritic cells (DCs) to promote a T helper type 2 lymphocyte (Th2) response in animal models. However, the mechanism behind this process remains unclear. In this study, we investigate the role of a nuclear factor for activated T-cells 1 (NFATc1) in the TSLP-induced polarisation towards a Th2 response. A cluster of differentiated (CD)14(+) peripheral blood mononuclear cells (PBMCs) and naive T cells were isolated from blood collected from healthy human volunteers, and TSLP was used to induce DC maturation. The effects of TSLP-DCs and treatments with FK506, an NFATc1 inhibitor, on naive T cell differentiation were monitored by measuring the interleukin (IL)-4, IL-13, and interferon-gamma (IFN-gamma) expression levels. In addition, the mRNA levels of T-box expression in T cells (T-bet), GATA binding protein 3 (GATA-3), TSLP, and NFATc1 were measured for the same purpose. IL-4, IL-13, and mRNA levels of GATA-3 and NFATc1 significantly increased with TSLP-DC induction (P<0.01), indicating polarization towards the Th2 response. These changes were reversed by treatment with FK506 (P<0.01). Our findings suggest that NFATc1 plays a key role in the TSLP-induced differentiation of T cells to Th2, and NFATc1 is a potential therapeutic target for treating allergic diseases. CI - (c) 2019 by the Association of Clinical Scientists, Inc. FAU - Li, Ya-Ting AU - Li YT AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Shen, Zhen-Yu AU - Shen ZY AD - Department of Pediatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Ling, Ye-Sheng AU - Ling YS AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Duan, Meng-Qi AU - Duan MQ AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Ye, Hui-Qing AU - Ye HQ AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Yang, Li-Fen AU - Yang LF AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Mai, You-Gang AU - Mai YG AD - Department of Pediatrics, Sun Yat-sen Memorial Hospital, Guangzhou, China chenzhuanggui@126.com. FAU - Chen, Zhuang-Gui AU - Chen ZG AD - Department of Pediatrics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China chenzhuanggui@126.com. LA - eng PT - Journal Article PL - United States TA - Ann Clin Lab Sci JT - Annals of clinical and laboratory science JID - 0410247 RN - 0 (CD14 protein, human) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (NFATC Transcription Factors) RN - 0 (NFATC1 protein, human) RN - 0 (TSLP protein, human) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - Cell Differentiation MH - Cell Polarity MH - Cells, Cultured MH - Cytokines/genetics/*metabolism/pharmacology MH - Dendritic Cells MH - Humans MH - Leukocytes, Mononuclear/cytology/metabolism MH - Lipopolysaccharide Receptors/metabolism MH - NFATC Transcription Factors/antagonists & inhibitors/genetics/*metabolism MH - Tacrolimus/pharmacology MH - Th1 Cells/drug effects/metabolism MH - Th2 Cells/*cytology/drug effects/metabolism OTO - NOTNLM OT - Dendritic cells OT - GATA-3 OT - T helper type 2 lymphocytes OT - nuclear factor of activated T-cells 1 OT - thymic stromal lymphopoietin EDAT- 2019/12/29 06:00 MHDA- 2020/06/23 06:00 CRDT- 2019/12/29 06:00 PHST- 2019/12/29 06:00 [entrez] PHST- 2019/12/29 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] AID - 49/6/722 [pii] PST - ppublish SO - Ann Clin Lab Sci. 2019 Nov;49(6):722-729.