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

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

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.

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.

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.