Dataset Information

The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and Treg cells.

ABSTRACT:

Background

This study aimed to investigate the role of aryl hydrocarbon receptor (AhR) and STAT3 gene during the differentiation of cluster of differentiation (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells.

Methods

First, CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one of the following treatments: Th17 group: antibodies against CD3 and CD28, 2.5?ng/mL transforming growth factor ? (TGF-?)1, 30?ng/mL interleukin (IL)-6, and 30?ng/mL IL-23; 6-formylindolo[3,2-b]carbazole (FICZ) group: antibodies against CD3 and CD28, 2.5?ng/mL TGF-?1, 30?ng/mL IL-6, 30?ng/mL IL-23, and 100?nM FICZ; FICZ + STAT3 RNAi group (shSTAT3 group): antibodies against CD3 and CD28, 2.5?ng/mL TGF-?1, 30?ng/mL IL-6, 30?ng/mL IL-23, 100?nM FICZ, and STAT3 RNAi; naphthoflavone group: antibodies against CD3 and CD28, 2.5?ng/mL TGF-?1, 30?ng/mL IL-6, 30?ng/mL IL-23, and 3 ?M naphthoflavone; 5) no antibodies were added in the control group. Later, the proportions of Th17 and Treg cells in each group were measured by flow cytometry; phospho-STAT3 and -STAT5 levels were measured by western blotting; and AhR, STAT3, STAT5, receptor-related orphan nuclear receptor ?t (ROR?t), FOXP3, T-cell receptor (TCR), CD25, IL-6R, IL-10, and IL-17 mRNA levels were also measured by real-time PCR.

Result

Th17 cells showed a rise and Treg cells showed a decrease in the FICZ group, but revised in the shSTAT3 group and the naphthoflavone group. Significant differences were observed in CD25, IL-6R, IL-10, and IL-17 mRNA levels among different groups.

Conclusion

STAT3 may cooperate with AhR to regulate the differentiation of both Th17 and Treg cells.

SUBMITTER: Liu X

PROVIDER: S-EPMC5413224 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and Treg cells.

Liu Xingxing X Hu Hui H Fan Heng H Zuo Dongmei D Shou Zhexing Z Liao Yi Y Nan Zhen Z Tang Qing Q

Medicine 20170401 17

<h4>Background</h4>This study aimed to investigate the role of aryl hydrocarbon receptor (AhR) and STAT3 gene during the differentiation of cluster of differentiation (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells.<h4>Methods</h4>First, CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one of the following treatments: Th17 group: antibodies against CD3 and CD28, 2.5 ng/mL tran ...[more]

PMID: 28445259

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Project description:In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-? signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs). In addition, in pulmonary PCM, the tolerogenic function of plasmacytoid dendritic cells was linked to the IDO1 activity. To further evaluate the function of IDO1 in pulmonary PCM, IDO1-deficient (IDO1-/-) C57BL/6 mice were intratracheally infected with P. brasiliensis yeasts and the infection analyzed at three postinfection periods regarding several parameters of disease severity and immune response. The fungal loads and tissue pathology of IDO1-/- mice were higher than their wild-type controls resulting in increased mortality rates. The evaluation of innate lymphoid cells showed an upregulated differentiation of the innate lymphoid cell 3 phenotype accompanied by a decreased expansion of ILC1 and NK cells in the lungs of infected IDO1-/- mice. DCs from these mice expressed elevated levels of costimulatory molecules and cytokine IL-6 associated with reduced production of IL-12, TNF-?, IL-1?, TGF-?, and IL-10. This response was concomitant with a marked reduction in AhR production. The absence of IDO1 expression caused an increased influx of activated Th17?cells to the lungs with a simultaneous reduction in Th1 and Treg cells. Accordingly, the suppressive cytokines IL-10, TGF-?, IL-27, and IL-35 appeared in reduced levels in the lungs of IDO1-/- mice. In conclusion, the immunological balance mediated by the axis IDO/AhR is fundamental to determine the balance between Th17/Treg cells and control the severity of pulmonary PCM.

Dataset Information

The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and Treg cells.

Background

Methods

Result

Conclusion

Publications

The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and Treg cells.

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