Regulatory T cells protect from autoimmune arthritis during pregnancy

Muñoz-Suano, Alba; Kallikourdis, Marinos; Sarris, Milka; Betz, Alexander G.

doi:10.1016/j.jaut.2011.09.007

Cited by 47 publications

(34 citation statements)

References 47 publications

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“…However, these cells are also detectable in peripheral blood and spleen of dams and are likely to provide systemic immune tolerance [14]. This has been conclusively demonstrated by adoptive transfer experiments, where T regs from pregnant mice, protected from collagen-induced arthritis, ameliorated autoimmunity in non-pregnant animals [15]. This also indicates that T regs are responsible for the pregnancyassociated recovery from arthritis.…”

Section: Pregnancy-induced Immunological Modulationsmentioning

confidence: 88%

Immunology of hepatic diseases during pregnancy

2016

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The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.

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Section: Pregnancy-induced Immunological Modulationsmentioning

confidence: 88%

Immunology of hepatic diseases during pregnancy

2016

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“…Foxp3 deficiency results in generalized autoimmune inflammation evident in scurfy mice (2)(3)(4)26) and in patients suffering from immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) (5,27). Beyond that, quantitative or functional Treg impairment has been described in a number of autoimmune diseases, including systemic lupus erythematosus (6,7,28,29), rheumatoid arthritis (8,30,31), and type I diabetes (9,10,32). In MS, Tregs were reported to possess diminished suppressive potential (11,33,34) and decreased expression of Foxp3 and immunosuppressive cytotoxic T lymphocyte antigen 4 (CTLA-4) (12,(35)(36)(37).…”

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confidence: 99%

Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy

Engler

Kursawe

Solano

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

123

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Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells. In vivo, T-cell-specific GR deletion in pregnant animals undergoing experimental autoimmune encephalomyelitis (EAE), the animal model of MS, resulted in a reduced Treg increase and a selective loss of pregnancy-induced protection, whereas reproductive success was unaffected. Our data imply that steroid hormones can shift the immunological balance in favor of Tregs via differential engagement of the GR in T cells. This newly defined mechanism confers protection from autoimmunity during pregnancy and represents a potential target for future therapy.multiple sclerosis | autoimmunity | pregnancy | Treg | steroid hormones R eproduction is fundamental to the maintenance and evolution of species. To ensure successful pregnancy, mothers have to establish robust immunological tolerance toward the semiallogeneic conceptus providing a secure niche for fetal development. Multiple mechanisms have evolved to prevent fetus-directed immune responses and alloreactive infiltration of the fetomaternal interface (1). These include creating a privileged local microenvironment that hampers T-cell priming and infiltration (2-4) but also imply global modulation of the immune system by pregnancy hormones and the shedding of fetal antigen into the mothers circulation (5).Intriguingly, pregnancy is also well known to suppress the inflammatory activity of a number of cell-mediated autoimmune diseases, including rheumatoid arthritis (6, 7), autoimmune hepatitis (8), and multiple sclerosis (MS) (9, 10). However, this beneficial effect is limited to the period of gestation and usually followed by a rebound of disease activity postpartum. In the case of MS, third trimester pregnancy leads to a remarkable reduction of the MS relapse rate (11), which exceeds the effects of most currently available disease-modifying drugs. Similarly, pregnancy as well as treatment with pregnancy hormones protect rodents from experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS (12) in both SJL/J and C57BL/6 mice (13-16), underpinning an interaction between pregnancy-related immune and endocrine adaptations and central nervous system (CNS) autoimmunity (17).The sensitive balance between conventional effector T cells (Tcons) and regulatory T cells (Tregs) has transpired as a common theme that connects reproductive biology and autoimmunity on a mechanistic level (18)(19)(20)(21). Tregs are characterized by the transcription factor forkhead box P3 (Foxp3) and effectively control effector responses mounted by Tcons in...

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“…This observation, in fact, helped lead Hench to the discovery of corticosteroids as the first treatment for RA [70]. In fact, Tregs play a major role in facilitating implantation of the embryo and maintaining the pregnancy despite the presence of "foreign" paternal antigens, effectively inducing tolerance to the developing fetus [71,72].…”

Section: T Regulatory Cellsmentioning

confidence: 99%

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Middleton¹

2012

J Clin Cell Immunol

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Rheumatoid arthritis is a common, well studied autoimmune disease characterized by a loss of self-tolerance. Current therapies have significantly advanced the successful treatment of the disease, but have been unsuccessful for a large number of patients. Furthermore, they have failed to induce long term medication free remission because they target a consequence of the disease, not the origins of a dis-regulated immune system. Current research is now focused on finding ways to correct and restore the balance of the immune system rather than just suppress it. The scientific foundations for a number of potential approaches to restoring immune tolerance already have been laid. This paper reviews a number of proposed targets for immunotherapy including vaccinations, shifting from Th1 to Th2 responses, molecules that promote the resolution of inflammation, tolerogenic dendritic cells, mesenchymal stem cells, and T regulatory cells. These strategies will hopefully allow a closer approach to a "cure" for this potentially devastating disease.

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Regulatory T cells protect from autoimmune arthritis during pregnancy

Cited by 47 publications

References 47 publications

Immunology of hepatic diseases during pregnancy

Immunology of hepatic diseases during pregnancy

Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

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