Recombinant human IL-37 inhibited endometriosis development in a mouse model through increasing Th1/Th2 ratio by inducing the maturation of dendritic cells

Lijie Li,Jianfa Jiang,Mingzhu Ye,Zhouzhou Liao

doi:10.1186/s12958-021-00811-3

Lijie Li, Jianfa Jiang + Show 2 more

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https://doi.org/10.1186/s12958-021-00811-3

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Abstract

BackgroundEndometriosis is a serious reproductive and general health consequences. Recombinant human IL-37 (rhIL-37) is an inhibitor of inflammation.MethodsELISA assay was performed to detect the concentration of cytokines. Flow cytometry was used to analyze cell proportion. Besides, qRT-PCR and western blotting assay were used to detect the level of gene and protein, respectively. Transwell co-culture system was used for the co-culture of dendritic cells (DCs) and CD4+T cells.ResultsOur data showed that rhIL-37 inhibited the development of ectopic lesions in the mice with endometriosis, increased Th1/Th2 ratio and induced DCs maturation. The co-culture system of DCs and CD4+T cells demonstrated that rhIL-37 increased Th1/Th2 cell ratio through promoting DCs maturation. Moreover, the expression of IL-4 in the DCs derived from healthy mice was inhibited by rhIL-37 treatment. rhIL-37 increased Th1/Th2 cell ratio through inhibiting IL-4 in DCs. Subsequently, our results proved that rhIL-37 promoted the maturation of DCs via inhibiting phosphorylation of STAT3. Activation of STAT3 could reverse rhIL-37-induced maturation of DCs.ConclusionOverall, rhIL-37 could protect against endometriosis through increasing the ratio of Th1/Th2 cells via inducing DCs maturation and inhibiting IL-4 expression in the DCs. Furthermore, rhIL-37 induced DCs maturation by inhibiting STAT3 phosphorylation. Our data confirmed the protective effect of rhIL-37 in endometriosis. These data may provide a novel idea for the treatment of the disease.Graphical abstract

Highlights

Endometriosis is a serious reproductive and general health consequences
Results Recombinant human IL-37 (rhIL-37) inhibited lesion development, increased serum Th1/Th2 ratio, and induced dendritic cells (DCs) maturation in the mice with endometriosis Here, compared with the mouse with endometriosis and normal saline-treated endometriosis mouse model, declined weight of ectopic lesion and reduced volume of ectopic lesions were found in the rhIL-37-treated endometriosis mouse model, suggesting that rh-IL-37 treatment effectively inhibited the development of ectopic lesions (Fig. 1A-C)
ELISA assay displayed that rhIL-37 was highly existed in the serum of the mice with endometriosis, and no rhIL-37 was found in the serum of control mice, endometriosis mouse model, and normal saline-treated endometriosis mouse model (Fig. 1D)

Summary

Introduction

Endometriosis is a serious reproductive and general health consequences. Recombinant human IL-37 (rhIL-37) is an inhibitor of inflammation. Li et al Reproductive Biology and Endocrinology (2021) 19:128 antagonists, aromatase inhibitors, and antiprogestins, could effectively protect against endometriosis, the treatment of the disease still is a challenge [4, 5]. It was demonstrated that the number of immature dendritic cells (iDCs) was notably higher than mature dendritic cells (mDCs) in the endometriosis tissues from a non-human primate model of the disease [13]. Fainaru et al revealed that immature bone marrow-derived DCs, not mature bone marrow-derived DCs, contribute to the development of endometriosis [14]. These studies suggested the important role of mDCs in the improvement of endometriosis

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