The TH 22-mediated IL-22 deficiency associated with premature ovarian insufficiency

Wenzhe Zhang; Shiru Xu; Rongrong Zhang; Zhuqing Li; Nianyu Li; Xiruo Zhang; Yueshuang Lu; Yuehong Bian; Ping Yang; Fang Fang; Yingying Qin; Xue Jiao

doi:10.1111/aji.13685

The T_H 22-mediated IL-22 deficiency associated with premature ovarian insufficiency

Am J Reprod Immunol. 2023 Apr;89(4):e13685. doi: 10.1111/aji.13685. Epub 2023 Feb 21.

Authors

Wenzhe Zhang^{1

2

3

4

5

6}, Shiru Xu^{1

2

3

4

5

6

7}, Rongrong Zhang^{1

2

3

4

5

6}, Zhuqing Li^{1

2

3

4

5

6}, Nianyu Li^{1

2

3

4

5

6}, Xiruo Zhang^{1

2

3

4

5

6}, Yueshuang Lu^{1

2

3

4

5

6}, Yuehong Bian^{1

2

3

4

5

6}, Ping Yang^{1

2

3

4

5

6}, Fang Fang^{1

2

3

4

5

6}, Yingying Qin^{1

2

3

4

5

6}, Xue Jiao^{1

2

3

4

5

6

8}

Affiliations

¹ Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China.
² Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China.
³ Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China.
⁴ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China.
⁵ Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China.
⁶ National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.
⁷ Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong, China.
⁸ Suzhou Research Institute, Shandong University, Suzhou, Jiangsu, China.

PMID: 36752193
DOI: 10.1111/aji.13685

Abstract

Research question: Is deficiency of IL-22 associated with premature ovarian insufficiency (POI)?

Design: Levels of IL-22 and IL-22BP, IL-22-producing T cells, and IL22RA1/IL10R2 expression were measured and compared among 29 patients with POI, 42 with precursor stage of POI (pre-POI) and 46 control women. Correlation of serum IL-22 and IL-22⁺ CD4⁺ T subsets with ovarian reserve markers were further analyzed.

Results: IL-22 levels in serum significantly differed among control women and patients with pre-POI and POI, with the lowest concentrations in POI group (p = .019). Significant reduction of peripheral CD4⁺ IL-22⁺ T cells was observed in patients with POI (p = .010), which mainly contributed by decrease of CD4⁺ IL-22⁺ IL-17^- T_H 22 cells (p = .012) but not T_H 17 cells (p = .125). Levels of serum IL-22 and IL-22-producing CD4⁺ T subsets were significantly correlated with ovarian reserve markers, including AMH, bilateral AFC, follicle-stimulating hormone (FSH), and E2 (p < .05). The specific receptor IL22RA1 expression was marginally reduced in granulosa cells from patients with pre-POI (p = .051). No difference of IL-22BP was observed either in serum (p = .216) or follicular fluid (p = .856) among groups.

Conclusions: Our study first demonstrated the significant association between T_H 22-mediated IL-22 deficiency and ovarian insufficiency, which provide new insights into the autoimmune disturbance and opens new avenues for exogenous IL-22 administration as potential intervention of POI.

Keywords: T helper 22 cell; interleukin 22; interleukin 22 receptor subunit alpha 1; ovarian reserve; premature ovarian insufficiency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Follicle Stimulating Hormone
Humans
Interleukin-22
Menopause, Premature*
Primary Ovarian Insufficiency*

Substances

Follicle Stimulating Hormone