Interleukin 22 prevents lipopolysaccharide- induced preterm labor in mice†

Abstract

Preterm birth is widespread and causes 35% of all neonatal deaths. Infants who survive face potential long-term complications. A major contributing factor of preterm birth is infection. We investigated the role of interleukin 22 (IL22) as a potential clinically relevant cytokine during gestational infection. IL22 is an effector molecule secreted by immune cells. While the expression of IL22 was reported in normal nonpregnant endometrium and early pregnancy decidua, little is known about uterine IL22 expression during mid or late gestational stages of pregnancy. Since IL22 has been shown to be an essential mediator in epithelial regeneration and wound repair, we investigated the potential role of IL22 during defense against an inflammatory response at the maternal-fetal interface. We used a well-established model to study infection and infection-associated inflammation during preterm birth in the mouse. We have shown that IL22 is upregulated to respond to an intrauterine lipopolysaccharide administration and plays an important role in controlling the risk of inflammation-induced preterm birth. This paper proposes IL22 as a treatment method to combat infection and prevent preterm birth in susceptible patients.

Microbiota-Dependent Effects of IL-22

“…Although little is known about the IL-22-dependent mechanisms implicated in the female genital tract regarding maintenance of ovarian and uterine function, it is assumed that IL-22 contributes significantly to female reproductive health and has a generally protective nature within this set of organs. Furthermore, IL-22 has been reported to play a role in combating sexually transmitted infections (STIs), intrauterine infections and also contributes to factors involved in pregnancy maintenance [ 112 , 113 , 114 ].…”

“…Uterine NK cells (uNK) also make up a large proportion of immune cells in decidual tissues during these two stages [ 118 ]. Interestingly, uNK cells have been found to produce IL-22 in the decidual tissues, and production is significantly upregulated in tissues of pregnant mice after local challenge with lipopolysaccharide (LPS), an unspecific endotoxin that stimulates immune reactions [ 113 , 114 ]. Another report by Gibbs et al has provided evidence that mucosal associated invariant T cells (MAIT) cells are present in cervical tissue, and are also responsible for upregulated IL-17 and IL-22 production in response to Escherichia coli [ 123 ].…”

“…Experiments involving intrauterine LPS injection resulted in preterm labor and pregnancy loss of all feti in IL-22-deficient mice. In these mice, administration of recombinant IL-22 prevented preterm birth and reduced apoptosis of placental cells [ 113 ]. Clinical studies support these findings, as patients with less IL-22 expression in uNK cells in the decidua were found to have higher rates of pregnancy loss [ 127 , 128 ].…”

Innate Lymphoid Cells at the Maternal-Fetal Interface in Human Pregnancy

“…Additionally, it is reported that decidual LTi-like cells may participate in the development of gestational diabetes and chronic diabetes via secreting IL-17 [86]. Recently, the effect of IL-22 in the prevention of lipopolysaccharide-induced preterm labor in mice was revealed and, thus, presents a potential protective role of decidual NCR + ILC3s in inflammation-induced preterm birth [171]. However, decidual ILC2s may play the opposite role in preterm birth due to the increase in ILC2s in the decidua basalis with spontaneous preterm labor compared to non-labor controls [46].…”

Interleukin‐22 promotes development of malignant lesions in a mouse model of spontaneous breast cancer

“…Interleukin-22 knockout (IL-22 À/À ) mice were laboratory-generated as described before (Dambaeva et al, 2018). For generating an IL-22 knockout spontaneous breast cancer mouse model, IL-22 wild-type (IL-22 +/+ ) or IL-22 À/À mice (C57/B6) were crossed with mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice (FVB; Jackson Laboratories, Bar Harbor, ME, USA).…”