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. 2020 Aug 9;13(8):100451.
doi: 10.1016/j.waojou.2020.100451. eCollection 2020 Aug.

MicroRNA-375-mediated regulation of ILC2 cells through TSLP in allergic rhinitis

Xi Luo  1 , Qingxiang Zeng  1 , Shengbao Yan  1 , Wenlong Liu  1 , Renzhong Luo  1
Affiliations

MicroRNA-375-mediated regulation of ILC2 cells through TSLP in allergic rhinitis

Xi Luo et al. World Allergy Organ J. .

Abstract

Background: Studies have shown that the number and function of type II innate lymphoid cells (ILC2) in peripheral blood of allergic rhinitis (AR) children increased significantly. This study aims to evaluate the role of miR-375 in the regulation of the differentiation and function of ILC2 through both in vivo and in vitro studies.

Methods: The expression of miR-375, thymic stromal lymphopoietin (TSLP) and the frequency of ILC2 were detected and compared between AR children and controls by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbnent assay (ELISA) and flow cytometry, respectively. The miR-375 mimics or inhibitors were transfected into human nasal epithelial cells (HNECs), and the production of TSLP was detected by ELISA. HNECs and ILC2s were co-cultured to explore the role of miR-375 on ILC2s. AR mice models were established to prove the effect of miR-375 on ILC2s in vivo.

Results: The expression of TSLP, miR-375, and the frequency of ILC2 were significantly higher in AR compared with controls. We found that the TSLP expression by HNECs were significantly higher when transfected with miR-375 mimics than in those transfected with miR-control and miR-375 inhibitor. In the coculture system, HNECs transfected with miR-375 mimics promote the type II cytokines production by ILC2, and this effect was blocked by anti-TSLP. Our results also showed that the miR-375 inhibitors attenuate allergic symptoms and production of type II cytokines in AR mice.

Conclusions: Our findings suggest that miR-375-mediated regulation of ILC2 cells through TSLP, providing new potential treatment target for AR.

Keywords: AR, Allergic rhinitis; Allergic rhinitis; ELISA, Enzyme-linked immunosorbnent assay; HNECs; HNECs, Human nasal epithelial cells; ILC2, Type II innate lymphoid cells; ILC2s; PCR, Real-time polymerase chain reaction; TSLP, Thymic stromal lymphopoietin; miR-375.

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Conflict of interest statement

The authors declare that they have no relevant conflicts of interest.

Figures

Fig. 1
Fig. 1
Elevated serum thymic stromal lymphopoietin (TSLP) (A), whole blood miR-375 (B), and type II innate lymphoid cells (ILC2) frequency (C) in peripheral blood mononuclear cells (PBMCs) in AR and the positive correlation between miR-375 and TSLP levels and ILC2 frequency (D,E) in children with AR
Fig. 2
Fig. 2
The expression of thymic stromal lymphopoietin (TSLP) by human nasal epithelial cell (HNECs) after transfected with miR-375 mimics, miR-control, miR-375 inhibitor or AG490 (JAK2-STAT3 inhibitor) in Figure A. The effect of Th2 cytokines on the expression of TSLP by HNECs was shown in Figure B. HDM, Dermatophagoides farinae
Fig. 3
Fig. 3
The expression of type II cytokines by type II innate lymphoid cells (ILC2) in the coculture system with human nasal epithelial cell (HNECs) in different combination of stimulators. AG490, JAK inhibitor. TSLP, thymic stromal lymphopoietin
Fig. 4
Fig. 4
The ovalbumin (OVA)-specific IgE level, frequency of nasal rubbing and sneezing, and the number of type II innate lymphoid cells (ILC2) cells in peripheral blood mononuclear cell (PBMCs) in allergic mice treated with miR-375 mimics, miR-375 inhibitors or anti-TSLP. TSLP, thymic stromal lymphopoietin
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