In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their “Yin and Yang” nature in a more comprehensive and coherent manner.

Problem Decline in myeloid‐derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation. Method of study Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G‐MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor ‐α (ER‐α), STAT‐3/pSTAT‐3, and caspase‐3, respectively. Results Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G‐MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER‐ α and increased caspase‐3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT‐3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT‐3 indicates that these processes pertaining to MDSCs are compromised. Conclusion Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal‐fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy.

Problem Vitamin D is well‐known for having anti‐inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre‐term birth. The present study aims to evaluate the impact of fetal cord serum 25‐hydroxyvitamin D‐mediated signaling in mediating inflammatory responses in placenta during pre‐term birth. Method of study For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre‐term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p‐NF‐kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study. Results Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre‐term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre‐term born babies. Conclusion Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti‐inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre‐term birth.

During pregnancy, maternal blood circulates through the intervillous space of the placenta and the reciprocal interactions between foetal tissues and maternal immune cells makes the intervillous space a unique immunological niche. Labour is characterised by a proinflammatory response in the myometrium, but the relationship between local and systemic changes during the onset of labour remains elusive. We here aimed to investigate how the systemic and intervillous circulatory systems are affected during labour from an immunological point of view. We report that the proportion of monocytes is dramatically higher in peripheral (PB), intervillous blood (IVB) and decidua in labouring (n = 14) compared to non-labouring women (n = 15), suggesting that labour leads to both a systemic and local mobilisation of monocytes. Labour was associated with a relative increase of effector memory T cells in the intervillous space compared to the periphery, and MAIT cells and T cells showed an elevated expression of activation markers both in PB and IVB. Intervillous monocytes consisted to a higher degree of CD14+CD16+ intermediate monocytes compared to peripheral monocytes, independently of mode of delivery, and displayed an altered phenotypic expression pattern. A proximity extension assay analysis of 168 proteins revealed that several proteins associated to myeloid cell migration and function, including CCL2 and M-CSF, were upregulated in IVB plasma in labouring women. Thus, the intervillous space could be a bridging site for the communication between the placenta and the periphery, which contribute to monocyte mobilisation and generation of inflammatory reactions during spontaneous labour.

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