TIPE2 Inhibits MGD Inflammation by Regulating Macrophage Polarization

Songjiao Zhao; Yankun Shen; Shinan Wu; Yi Shao; Ruize Shi; Yan Yan; Hui Zhao

doi:10.3390/jpm13030492

TIPE2 Inhibits MGD Inflammation by Regulating Macrophage Polarization

J Pers Med. 2023 Mar 9;13(3):492. doi: 10.3390/jpm13030492.

Authors

Songjiao Zhao^{1

2

3

4

5}, Yankun Shen⁶, Shinan Wu⁶, Yi Shao⁶, Ruize Shi^{1

2

3

4

5}, Yan Yan^{1

2

3

4

5}, Hui Zhao^{1

2

3

4

5}

Affiliations

¹ Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
² National Clinical Research Center for Eye Diseases, Shanghai 200080, China.
³ Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China.
⁴ Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China.
⁵ Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China.
⁶ Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Abstract

Background: The aim of this study was to decide the role of the polarization of macrophages regulated by tumor necrosis factor-α (TNF-α)-induced protein 8-like 2 (TIPE2) in meibomian gland dysfunction (MGD).

Methods: Firstly, the secretory function of the meibomian gland (MG) in apolipoprotein E knockout (ApoE^-/-) MGD mice and normal mice was detected by oil red staining. Then, the expression levels of markers of M1 and M2 macrophages were detected by immunofluorescence staining in MGD, normal mice, and mild and severe MGD corpses to decide the role of M1 and M2 macrophages in MGD inflammation. Meanwhile, the expression levels of TIPE2 in MGD mice and MGD patients were detected by immunofluorescence staining, and the correlations among TIPE2, M1 and M2 macrophages were analyzed by immunofluorescence double staining in MGD mice and MGD patients. Furthermore, lipopolysaccharide (LPS) and interleulkin-4 (IL-4) were used to induce M1 and M2 polarization of macrophages, and the mRNA level of TIPE2 was detected in M1 and M2 macrophages.

Results: Oil red staining showed that eyelid fat congestion was more severe in (ApoE^-/-) MGD mice than in normal mice, and the M1 macrophage was the primary inflammatory cell infiltrated in (ApoE^-/-) MGD mice (p < 0.05). The results of the immunofluorescence staining showed that the infiltration of macrophages in MGD mice was more obvious than that in the normal group, and M1 macrophage was the dominant group (p < 0.05). Similar to the results of the MGD mouse model, more macrophage infiltration was observed in MGD patients' MG tissues, and there were more M1 cells in the severe group than in the mild group (p < 0.05). Moreover, the expression of TIPE2 was positively correlated with the expression of M2 macrophages in MGD patients and mice MG tissues (p < 0.05). The expression of TIPE2 mRNA in LPS-induced M1 macrophages declined, while the expression of TIPE2 mRNA in IL-4-induced M2 macrophages increased (p < 0.05).

Conclusion: M1 macrophage was the dominant group infiltrated in the MG tissue of MGD, and TIPE2 is a potential anti-inflammatory target for preventing the development of MGD by promoting the M2 polarization of macrophages.

Keywords: TIPE2; macrophage; meibomian gland dysfunction; polarization.

Grants and funding

YG2023ZD18/Shanghai Jiao Tong University