Treg cells in autoimmunity: from identification to Treg-based therapies

Göschl, Lisa; Scheinecker, Clemens; Bonelli, Michael

doi:10.1007/s00281-019-00741-8

Cited by 138 publications

(109 citation statements)

References 237 publications

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“…Foxp3 + Treg are endowed with plasticity that enables them to specialize in selectively regulating effector T cell responses ( 38 ). Several of the genes dependent of the IL-1β pathways that showed enhanced expression in Treg after interaction with MPP, including Ifng (IFN-γ), Tbx21 ( 39 ), and Ccl5 ( 20 ), have been reported to confer to Treg the capacity to suppress Th1 and Th17 inflammatory cells, most appropriate to control EAE disease.…”

Section: Discussionmentioning

confidence: 99%

Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis

et al. 2020

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Achieving immunoregulation via in vivo expansion of Foxp3+ regulatory CD4+ T cells (Treg) remains challenging. We have shown that mobilization confers to multipotent hematopoietic progenitors (MPPs) the capacity to enhance Treg proliferation. Transcriptomic analysis of Tregs co-cultured with MPPs revealed enhanced expression of genes stabilizing the suppressive function of Tregs as well as the activation of IL-1β–driven pathways. Adoptive transfer of only 25,000 MPPs effectively reduced the development of experimental autoimmune encephalomyelitis (EAE), a pre-clinical model for multiple sclerosis (MS). Production of the pathogenic cytokines IL-17 and GM-CSF by spinal cord-derived CD4+ T-cells in MPP-protected recipients was reduced while Treg expansion was enhanced. Treg depletion once protection by MPPs was established, triggered disease relapse to the same level as in EAE mice without MPP injection. The key role of IL-1β was further confirmed in vivo by the lack of protection against EAE in recipients of IL-1β–deficient MPPs. Mobilized MPPs may thus be worth considering for cell therapy of MS either per se or for enrichment of HSC grafts in autologous bone marrow transplantation already implemented in patients with severe refractory multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis

et al. 2020

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“…It is known that CD25+ T cells exert regulatory functions but can also (re)gain effector functions. However, it is well accepted that T-cell populations expressing the transcription factor forkhead box protein 3 (Foxp3) constitute T-cell lineages with suppressive functions [31,32]. With respect to this, our study is limited since it did not investigate Treg populations expressing Foxp3 which could have been differently affected by the antibiotic treatment.…”

Section: • Fibroblastsmentioning

confidence: 98%

Lessons from mouse models of Graves’ disease

et al. 2020

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Graves' disease (GD) is an autoimmune condition with the appearance of anti-TSH receptor (TSHR) autoantibodies in the serum. The consequence is the development of hyperthyroidism in most of the patients. In addition, in the most severe cases, patients can develop orbitopathy (GO), achropachy and dermopathy. The central role of the TSHR for the disease pathology has been well accepted. Therefore immunization against the TSHR is pivotal for the creation of in vivo models for the disease. However, TSHR is well preserved among the species and therefore the immune system is highly tolerant. Many differing attempts have been performed to break tolerance and to create a proper animal model in the last decades. The most successful have been achieved by introducing the human TSHR extracellular domain into the body, either by injection of plasmid or adenoviruses. Currently available models develop the whole spectrum of Graves' disease-autoimmune thyroid disease and orbitopathy and are suitable to study disease pathogenesis and to perform treatment studies. In recent publications new immunomodulatory therapies have been assessed and also diseaseprevention by inducing tolerance using small cyclic peptides from the antigenic region of the extracellular subunit of the TSHR.

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“…In contrast to T effector cells, Tregs are key negative regulators of inflammation that promote immune tolerance (45). Several studies have described reduced Treg frequency in AAV, but others have reported increased numbers, possibly due to the different methodologies of identifying human Tregs (36,(46)(47)(48)(49)(50).…”

Section: T Cells In Anca-associated Vasculitismentioning

confidence: 99%

T Cells in Autoimmunity-Associated Cardiovascular Diseases

et al. 2020

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T cells are indisputably critical mediators of atherosclerotic cardiovascular disease (CVD), where they secrete pro-inflammatory cytokines that promote vascular pathology. Equally well-established is the fact that autoimmune diseases, which are mediated by autoreactive T cells, substantially increase the risk of developing CVD. Indeed, as immunomodulatory treatments have become more effective at treating end-organ pathology, CVD has become a leading cause of death in patients with autoimmune diseases. Despite this, investigators have only recently begun to probe the mechanisms by which autoreactive T cells promote CVD in the context of autoimmune diseases. T cells are best-studied in the pathogenesis of systemic vasculitides, where they react to selfantigen in the vessel wall. However, newer studies indicate that T cells also contribute to the increased CVD risk associated with lupus and rheumatoid arthritis. Given the central role of T-cell-derived cytokines in the pathogenesis of psoriasis, the role of these factors in psoriatic CVD is also under investigation. In the future, T cells are likely to represent major targets for the prevention and treatment of CVD in patients with autoimmune diseases.

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Treg cells in autoimmunity: from identification to Treg-based therapies

Cited by 138 publications

References 237 publications

Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis

Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis

Lessons from mouse models of Graves’ disease

T Cells in Autoimmunity-Associated Cardiovascular Diseases

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