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

Abstract

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- TH 22 cells (p=.012) but not TH 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 TH 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.