Journal
EXPERIMENTAL CELL RESEARCH
Volume 398, Issue 1, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2020.112393
Keywords
TSLP; Exosomes; Th17 cells; Tregs; Fungal keratitis
Categories
Funding
- Foreign Science and Technology Cooperation Project of Science and Technology Department in Anhui Province, China [201904b11020042]
- Natural Science Foundation of Anhui [1908085MH253]
Ask authors/readers for more resources
This study demonstrates that TSLP regulates the differentiation of Th17 and Treg cells by controlling miR-21 and Smad7, revealing the biological role of miR-21 in fungal keratitis.
Thymic stromal lymphopoietin (TSLP) is associated with fungal keratitis. This work aims to investigate whether TSLP can regulate T helper (Th) 17 and regulatory T cell (Treg) differentiation. We separated dendritic cells (DCs) from peripheral blood of healthy volunteers. DCs were treated with TSLP to activate DCs, and exosomes were obtained. CD+ T cells were incubated with exosomes from TSLP-treated DCs. We found that exosomes from TSLP-treated DCs notably promoted the proportions of Th17 cells and inhibited the proportions of Tregs in the CD4(+) T cells. Moreover, exosomes from TSLP-treated DCs enhanced the expression of retinoid-related orphan receptor gamma t (ROR gamma t) and interleukin 17 (IL-17), and repressed the expression of forkhead box protein P3 (Foxp3) and interleukin 10 (IL-10) in the CD4(+) T cells. Furthermore, miR-21 was highly expressed in exosomes from TSLP-treated DCs. Exosomes from TSLP-treated miR-21-silenced DCs promoted Treg differentiation and suppressed Th17 differentiation. Smad7 up-regulation repressed Th17 differentiation and enhanced Treg differentiation, which was abolished by miR-21 overexpression. Smad7 overexpression rescued the effect of exosomes from TSLP-treated DCs on Th17/Treg differentiation. In conclusion, our article confirms that TSLP induces DCs to deliver miR-21 by secreting exosomes, and thus miR-21 regulates Th17/Treg differentiation by inhibiting Smad7. Thus, this work further reveals the biological role of miR-21 in fungal keratitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available