The Role of Peritoneal Immunity in Peritoneal Endometriosis and Related Infertility

Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms

METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells

Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells