Human chorionic gonadotropin prevents Sjögren's syndrome–like exocrinopathy in mice

Li, Na; Shigihara, Toshikatsu; Tzioufas, Athanasios G.; Notkins, Abner Louis; Yoon, Ji‐Won; Lee, Youn-Jung

doi:10.1002/art.22737

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…While hCG plays a critical role in the sustenance of human pregnancy (11, 36, 37), binding sites for hCG on non-reproductive tissues (12–14, 38) are suggestive of additional functions, including immune modulation. Indeed, the administration of hCG prevents (or reduces the severity of) T cell-mediated autoimmune conditions in mice and humans (17, 18, 39, 40), a finding of some interest, given that pregnancy is associated with an amelioration of the symptoms of Th1-associated autoimmune diseases (9, 10).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from organs of the reproductive system, receptors for hCG are also present in extra-gonadal tissues including T cells (12), B cells (13), and macrophages (14), suggesting the hormone may have as yet un-discovered effects. Its roles in mediating feto-maternal immune tolerance (15, 16) and postulated immunosuppressive activity has prompted investigation of its effects in animal models of organ-specific (Th1-mediated) autoimmunity; administration of hCG ameliorates symptoms in spontaneous murine models of Type-1 diabetes (17) and Sjögren's Syndrome (18).…”

Section: Introductionmentioning

confidence: 99%

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Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses

Sachdeva

Bose

et al. 2018

Front. Endocrinol.

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Immunopathological outcomes in Systemic Lupus Erythematosus (SLE; or lupus) are believed to be autoantibody-mediated. Conditions which promote a Th2 skew (such as pregnancy) should encourage antibody production, worsening antibody-mediated diseases while ameliorating Th1/Th17-mediated diseases. Although an increased propensity toward autoreactivity can be observed in pregnant lupus patients and in pregnant lupus-prone mice, whether a unique human pregnancy-specific factor can contribute to such effects is unknown. This study assessed whether human chorionic gonadotropin (hCG, a pregnancy-specific hormone of diverse function) at physiological concentrations could mediate stimulatory influences on immune parameters in non-pregnant, lupus-prone mice, in light of the hormone's ameliorating effects on Th1-mediated autoimmunity in murine models. Results demonstrate that administration of hCG heightened global autoreactivity in such mice; antibodies to dsDNA, RNP68, Protein S, Protein C, β2-glycoprotein 1, and several phospholipids were enhanced, and hormone administration had adverse effects on animal survival. Specifically in splenic cell cultures containing cells derived from lupus-prone mice, hCG demonstrated synergistic effects with TLR ligands (up-modulation of costimulatory markers on B cells) as well as with TCR stimuli (enhanced proliferative responses, enhanced levels of cytokines, and the phosphorylation of p38). In both instances, enhanced synthesis of lupus-associated cytokines was observed, in addition to the heightened generation of autoantibodies reactive toward apoptotic blebs. These results suggest that selective transducive, proliferative, and differentiative effects of hCG on adaptive immune cells may drive autoreactive responses in a lupus environment, and may also potentially provide insights into the association between the presence of higher hCG levels (or the administration of hCG) with the presence (or appearance) of humoral autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses

Sachdeva

Bose

et al. 2018

Front. Endocrinol.

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“…Earlier, we showed that hCG can inhibit the development of diabetes in NOD mice [9] and LPS-induced SIRS [10]. It has been shown recently that hCG prevents the development of Sjögren's syndrome-like salivary gland exocrinopathy in mice [11].…”

Section: Introductionmentioning

confidence: 97%

Chorionic gonadotropin alleviates thioglycollate-induced peritonitis by affecting macrophage function

Wan

Coppens

Helden-Meeuwsen

et al. 2009

Journal of Leukocyte Biology

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Human chorionic gonadotrophin (hCG) is a hormone produced during pregnancy and present at the implantation site and in the maternal blood. Pregnancy has been proposed to represent a controlled state of inflammation at an early stage at the implantation site and later, systemically extended to the maternal circulation. Earlier, we reported that hCG can inhibit the development of diabetes in NOD mice and LPS-induced septic shock in a murine model. We hypothesize that hCG can contribute to the reduction of inflammation by modifying Mphi function. Here, the TG-induced peritonitis model for inflammation was used to investigate the effect of hCG on cytokine production and cell recruitment in vivo. hCG pretreatment in TG-induced peritonitis increased the number of peritoneal cells, especially PMN and monocytes, compared with mice injected with TG only. This increased cell number was partially explained by increased cell survival induced by hCG. Despite the cellular infiltrate, hCG pretreatment decreased i.p. TNF-alpha, IL-6, PTX3, CCL3, and CCL5 levels. By depleting peritoneal resident Mphi using clodronate liposomes prior to the application of hCG and the TG trigger, we established that Mphi are the main responsive cells to hCG, as the suppressed TNF-alpha and IL-6 production and increased PMN influx are abolished in their absence. Together, these data suggest that hCG contributes to the controlled inflammatory state of pregnancy by regulating Mphi proinflammatory function.

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“…Indeed, pregnancy is associated with an improvement in autoimmune disease symptoms associated with a Th1 profile (114,115). The administration of hCG prevents (or decreases the severity) T-cell mediated autoimmune diseases in mice and humans (86,(116)(117)(118).…”

Section: Hcg and Autoimmune Diseasesmentioning

confidence: 99%

Human Chorionic Gonadotrophin: New Pleiotropic Functions for an “Old” Hormone During Pregnancy

et al. 2020

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Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hCG RNA is transcribed as early as the eight-cell stage, and the blastocyst produces the protein before its implantation. hCG in the uterine microenvironment binds with its cognate receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), on the endometrial surface. This binding stimulates leukemia inhibitory factor (LIF) production and inhibits interleukin-6 (IL-6) production by epithelial cells of the endometrium. These effects ensure essential help in the preparation of the endometrium for initial embryo implantation. hCG also effects angiogenic and immunomodulatory actions as reported in many articles by our laboratories and other ones. By stimulating angiogenesis and vasculogenesis, hCG provides the placenta with an adequate maternal blood supply and optimal embryo nutrition during the invasion of the uterine endometrium. The immunomodulatory properties of hCG are numerous and important for programming maternal immune tolerance toward the embryo. The reported effects of hCG on uterine NK, Treg, and B cells, three major cell populations for the maintenance of pregnancy, demonstrate the role of this embryonic signal as a crucial immune regulator in the course of pregnancy. Human embryo rejection for hCG-related immunological reasons has been studied in different ways, and a sufficient dose of hCG seems to be necessary to maintain maternal tolerance. Different teams have studied the addition of hCG in patients suffering from recurrent miscarriages or implantation failures. hCG could also have a beneficial or a negative impact on autoimmune diseases during pregnancy. In this review, we will discuss the immunological impacts of hCG during pregnancy and if this hormone might be used therapeutically.

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Human chorionic gonadotropin prevents Sjögren's syndrome–like exocrinopathy in mice

Cited by 10 publications

References 21 publications

Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses

Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses

Chorionic gonadotropin alleviates thioglycollate-induced peritonitis by affecting macrophage function

Human Chorionic Gonadotrophin: New Pleiotropic Functions for an “Old” Hormone During Pregnancy

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