GM-CSF-Dependent Inflammatory Pathways

Hamilton, John A.

doi:10.3389/fimmu.2019.02055

Cited by 109 publications

(118 citation statements)

References 104 publications

(133 reference statements)

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“…By example, the importance of myeloid-derived immune cells and activities for cervix remodeling was emphasized in a recent study in mice that used antibody treatment to suppress the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) and block LPS-induced preterm birth (145). GM-CSF acts to reduces myeloid cell migrations, stimulates their differentiation, and proinflammatory activities (146). With relevance for women at high risk for preterm birth as well, findings indicate that inflammatory proteins increased in amniotic fluid before premature delivery (123).…”

Section: Immunobiologic Perspective On Cervix Remodeling With Pretermmentioning

confidence: 99%

Immunobiology of Cervix Ripening

Yellon

2020

Front. Immunol.

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The cervix is the essential gatekeeper for birth. Incomplete cervix remodeling contributes to problems with delivery at or post-term while preterm birth is a major factor in perinatal morbidity and mortality in newborns. Lack of cervix biopsies from women during the period preceding term or preterm birth have led to use of rodent models to advanced understanding of the mechanism for prepartum cervix remodeling. The critical transition from a soft cervix to a compliant prepartum lower uterine segment has only recently been recognized to occur in various mammalian species when progesterone in circulation is at or near the peak of pregnancy in preparation for birth. In rodents, characterization of ripening resembles an inflammatory process with a temporal coincidence of decreased density of cell nuclei, decline in cross-linked extracellular collagen, and increased presence of macrophages in the cervix. Although a role for inflammation in parturition and cervix remodeling is not a new concept, a comprehensive examination of literature in this review reveals that many conclusions are drawn from comparisons before and after ripening has occurred, not during the process. The present review focuses on essential phenotypes and functions of resident myeloid and possibly other immune cells to bridge the gap with evidence that specific biomarkers may assess the progress of ripening both at term and with preterm birth. Moreover, use of endpoints to determine the effectiveness of various therapeutic approaches to forestall remodeling and reduce risks for preterm birth, or facilitate ripening to promote parturition will improve the postpartum well-being of mothers and newborns. The maternal immune system in mammals adapts to tolerate the differentiation of novel structures associated with the fetal allograft. Development of two interfaces protect the fetus from rejection and assault by the ecology of the external environment. The internal fetal-maternal interface, as represented by the fetal membranes, placenta, and decidua, is crucial for maintaining maternal inflammatory reactivity for surveillance and responses to pathogens. Discussion of the internal interface is elsewhere and in this special volume (1-3). However, the present review is focused on the external fetal-maternal interface consisting of an amniotic fluid buffer, in a forebag region later in pregnancy as the fetal head engages the lower uterus, and the fetal membranes as they press against the internal os of the cervix. This description of a singleton pregnancy in primates near term applies to rodents, despite anatomical differences in the uterus described below, because observations indicate a single fetal sac engages the internal os of the cervix shortly before labor. The success of this external interface to fend off the biome and virome in the vagina reflects the barrier function of the cervix to protect both the fetus and maternal host structures in the uterus. The cervix barrier function has both immunological and structural components. One part of the mate...

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Section: Immunobiologic Perspective On Cervix Remodeling With Pretermmentioning

confidence: 99%

Immunobiology of Cervix Ripening

Yellon

2020

Front. Immunol.

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“…Granulocyte-macrophage colony-simulating factor (GM-CSF), originally identified as a hematopoietic growth factor has been recently identified as a prominent factor playing role in inflammation and autommunity [44,45]. This cytokine apparently plays an important role in the pathogenesis of MS, especially in modulation of myeloid cell function and potentially direct triggering of tissue destruction by these cells [46].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

et al. 2020

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Background: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDLcholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis.Methods: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colonystimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. Results: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls.Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. Conclusion:Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS.

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“…MsrB1 may also control macrophage immune activities: MsrB1 ablation in bone marrow-derived macrophages promote their M-CSF-induced production of anti-inflammatory cytokines [ 17 ]. The ability of MsrB1 to stimulate the production of proinflammatory cytokines in DCs while driving anti-inflammatory cytokine production in macrophages may reflect the fact that GM-CSF and M-CSF, respectively, induce pro- and anti-inflammatory functions in myeloid cells [ 45 ]. These observations suggest that MsrB1 may have different effects depending on the target cell type and local conditions.…”

Section: Discussionmentioning

confidence: 99%

The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses

et al. 2020

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Immune activation associates with the intracellular generation of reactive oxygen species(ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidenceshows that ROS‐mediated signal transduction can be regulated by selenoproteins such asmethionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunityremains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability ofdendritic cells (DCs) to provide the antigen presentation and costimulation that are needed forcluster of differentiation antigen four (CD4) T‐cell priming in mice. We found that MsrB1 regulatedsignal transducer and activator of transcription‐6 (STAT6) phosphorylation in DCs. Moreover, bothin vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)‐induced Interleukin‐12 (IL‐12)production by DCs and drove T‐helper 1 (Th1) differentiation after immunization. We propose thatMsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL‐12production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promotedfollicular helper T‐cell (Tfh) differentiation when mice were immunized with sheep red blood cells.This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control ofadaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controllingimmune reactions.

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GM-CSF-Dependent Inflammatory Pathways

Cited by 109 publications

References 104 publications

Immunobiology of Cervix Ripening

Immunobiology of Cervix Ripening

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses

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