Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia

Abstract

Th (T helper) cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM) has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs).

Th1/Th2 Dichotomy in Obese Women with Gestational Diabetes and Their Macrosomic Babies

“…T cells (responsible for cell-mediated immunity) have been shown to play a critical role in GDM and macrosomia [ 13 , 17 , 18 ]. T cells can be divided into two subsets: T helper cells (CD4+) and T cytotoxic cells (CD8+).…”

“…They observed a very high level of proinflammatory cytokines, IFNg and IL2, in obese and diabetic animals [ 18 ]. In gestational diabetic women, some authors have shown that low Th1 concentrations and high IL-10 levels may be implicated in maintaining the pregnancy [ 13 , 17 , 20 ]. Besides, recent data have suggested the protective role of IL-10 against inflammation in adipose tissue and insulin resistance [ 37 – 39 ].…”

“…Furthermore, some authors [ 17 , 40 ] have reported spontaneous abortion cases and patients with recurrent miscarriage are associated with lower systemic IL-10 compared to normal pregnancies. Jasper et al [ 41 ] have shown that adoptive transfer of T lymphocytes depleted of Treg cells in pregnant T cell-deficient mice led to a failure of gestation due to immunological rejection of the fetus [ 17 , 41 ].…”

“…Differentiation of Th cells into Th1 and Th2 cells involves the activation of Th1 and Th2 transcription factors, T-bet and GATA3, respectively [ 14 , 15 ]. It has been reported that abnormalities of humoral and cell-mediated immunity in type I diabetic women during pregnancy may complicate immune-fetal interaction leading to fetal overgrowth and alteration in the immune system of a newborn which persist till adulthood [ 16 , 17 ].…”

Calcifediol Decreases Interleukin-6 Secretion by Cultured Human Trophoblasts From GDM Pregnancies

“…In contrast to GDM-d, we found no differences in protein expression for any of the vitamin D metabolic components between GDM-i and NG placental tissues. The lack of difference between GDM-i and NG groups could be explained by the anti-inflammatory properties of insulin [50, 51]. It is possible that the inflammatory state is decreased at the feto-maternal interface in GDM-i women compared with GDM-d women.…”