Abstract
Although the concepts related to fetal immune tolerance proposed by Sir Peter Medawar in the 1950s have not withstood the test of time, they revolutionized our current understanding of the immunity at the maternal-fetal interface. An important extension of the original Medawar paradigm is the investigation into the underlying mechanisms for adverse pregnancy outcomes, including recurrent spontaneous abortion, preterm birth, preeclampsia and gestational diabetes mellitus (GDM). Although a common pregnancy complication with systemic symptoms, GDM still lacks understanding of immunological perturbations associated with the pathological processes, particularly at the maternal-fetal interface. GDM has been characterized by low grade systemic inflammation that exacerbates maternal immune responses. In this regard, GDM may also entail mild autoimmune pathology by dysregulating circulating and uterine regulatory T cells (Tregs). The aim of this review article is to focus on maternal-fetal immunological tolerance phenomenon and discuss how local or systemic inflammation has been programmed in GDM. Specifically, this review addresses the following questions: Does the inflammatory or exhausted Treg population affecting the Th17:Treg ratio lead to the propensity of a pro-inflammatory environment? Do glycans and glycan-binding proteins (mainly galectins) contribute to the biology of immune responses in GDM? Our understanding of these important questions is still elementary as there are no well-defined animal models that mimic all the features of GDM or can be used to better understand the mechanistic underpinnings associated with this common pregnancy complication. In this review, we will leverage our preliminary studies and the literature to provide a conceptualized discussion on the immunobiology of GDM.
Highlights
Obesity, diabetes, insulin treatment, stress, and hypertension are words that attract the general public’s attention
We have presented a comprehensive overview of the literature on gestational diabetes mellitus (GDM) and proposed new ideas with discussion of our experimental strategy to better understand the GDM etiology
We highlight the fact that the maternal-fetal tolerance choreography is not a uniform event in normal pregnancy vs. adverse pregnancy outcomes such as GDM
Summary
Diabetes, insulin treatment, stress, and hypertension are words that attract the general public’s attention. Most studies highlight a nexus between excessive free glucose, gut microbiota, inflammation and dysregulated functions of immune cell types that contribute to programming of GDM [32,33,34]. A. Inflammation: Recent evidence suggests that GDM is an issue of increased insulin resistance and glucose intolerance, and a condition of low-grade systemic and placental inflammation [39].
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