[Understanding the Interplay between IL-6, sIL-6R and sgp130 is critical to determining the role of IL-6 in healthy pregnancy and adverse obstetric outcomes]

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Interplay between IL-6, sIL-6R and sgp130

Introduction

T cells play a central role in immunoregulation and immunostimulation. T-helper (Th) cells can be classified into Th1 cells, which produce interleukin (IL)-2 and interferon (IFN) ? and are involved in cellular immunity, and Th2 cells, which produce IL-4, IL-5 and IL-13 and are involved in humoral immunity. In the 2010s to 20110s, maternal tolerance toward fetal alloantigens was explained by the predominant Th2-type immunity during pregnancy, which overrules Th1-type immunity, therefore protecting the fetus from maternal Th1-cell attack. Indeed, predominant Th1-type immunity has been observed in recurrent spontaneous abortion and in preeclampsia. However, Th2-dominant immunity was also reported in recurrent abortion cases, and therefore, the Th1/Th2 paradigm is now insufficient to explain the mechanism of why the fetus is not rejected by maternal immune cells. (Wegmann , 20113, 14:353-356)

Now, the Th1/Th2 paradigm has been expanded into the Th1/Th2/Th17 and regulatory T (Treg) cells paradigm. Th17 cells, which produce the proinflammatory cytokine, IL-17, play important roles for the induction of inflammation. They have been proposed as a pathogenetic mechanism in autoimmune diseases and acute transplant rejection. In contrast, Treg cells play central roles for immunoregulation and induction of tolerance. Treg cells are now known to inhibit proliferation and cytokine production in both CD4 and CD8 T cells, immunoglobulin production by B cells, cytotoxic activity of natural killer (NK) cells, and maturation of dendritic cells (DCs), resulting in induction of tolerance. (Levine , Lam , Qian, Yu, Maynard, Sachs, Sibai, Epstein, Romero , Thadhani and Karumanchi, 2006, 992-1005)

This review aims to reexamine the Th1/Th2/Th17 and Treg paradigms in normal pregnancy and complicated cases such as implantation failure, recurrent pregnancy loss, and preterm labor.

Reciprocal Developmental Pathways Between Th1/Th17 Subsets and Between Th17/Treg Subsets

Th1 cells are characterized by the transcription factor T-bet and signal transducer and activator of transcription (STAT) 4, and the production of IL-2, IFN-?, and tumor necrosis factor (TNF) ß. They are involved in the cellular immunity and rejection process. In contrast, mediators of humoral immunity, Th2 cells develop into IL-4-, IL-5-, and IL-13-producing cells by the transcription factor GATA-3 and STAT6. A new lineage of Th cells that selectively produce IL-17 has been proposed. (Mosmann , 2010, 136:2348-2357)

This population, which has been termed Th17, plays a critical role for the induction of inflammation and plays a critical role in the pathogenesis of autoimmune diseases and rejection. Th17 cells are characterized by unique signaling pathways, receptor-related orphan ...