title: Interleukin-10: a pleiotropic regulator in pregnancy.
abstract: Pregnancy is a unique and well-choreographed physiological process that involves intricate interplay of inflammatory and anti-inflammatory milieu, hormonal changes, and cellular and molecular events at the maternal-fetal interface. IL-10 is a pregnancy compatible cytokine that plays a vital role in maintaining immune tolerance. A wide array of cell types including both immune and non-immune cells secret IL-10 in an autocrine and paracrine manner. IL-10 binds to a specific receptor complex and activates JAK-STAT and PI3K-Akt signaling pathways while inhibiting NF-κB signaling pathway. IL-10 exerts its anti-inflammatory effects mainly by decreasing pro-inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-α, by inducing heme oxygenase-1, and by inhibiting antigen presentation via blocking major histocompatibility complex (MHC) class II expression. Prior studies from our group and others have shown that IL-10 also functions as a potent protector against vascular dysfunction, and enhancement of IL-10 may serve as an immunotherapeutic intervention to treat adverse pregnancy outcomes. This review seeks to critically evaluate the archetypal functions of IL-10 as an immune suppressive factor as well as its novel functions as a vascular protector and modulator of endoplasmic reticulum (ER) stress and autophagy in the context of normal and adverse pregnancy outcomes.
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology*; D053612:Janus Kinases / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; C508609:IL10 protein, human; D050791:STAT Transcription Factors; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Adverse pregnancy outcomes; angiogenesis; autophagy; endoplasmic reticulum stress; immune tolerance; preeclampsia