Decitabine revives Treg function in ITP

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

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Age-Related Changes in Thymic Central Tolerance

Frontiers in Immunology ◽

10.3389/fimmu.2021.676236 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jayashree Srinivasan ◽

Jessica N. Lancaster ◽

Nandini Singarapu ◽

Laura P. Hale ◽

Lauren I. R. Ehrlich ◽

...

Keyword(s):

T Cells ◽

Negative Selection ◽

Thymic Epithelial Cells ◽

Central Tolerance ◽

Adult Transition ◽

Treg Function ◽

Age Related ◽

And Function ◽

Antigen Presenting ◽

Age Related Changes

Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance. In keeping with this possibility, there are age-associated changes in the cellular composition and function of T cells and Treg. This review summarizes changes in T cell and Treg function during the perinatal to adult transition and in the course of normal aging, and relates these changes to age-associated alterations in thymic HAPC and TEC subsets.

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The novel ability of a tyrosine kinase inhibitor to alter myeloid-derived suppressor cell and t-regulatory cell (Treg) function

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2012.06.346 ◽

2012 ◽

Vol 215 (3) ◽

pp. S134

Author(s):

Brian A. Coakley ◽

David Z. Kalir ◽

Ge Ma ◽

Junko Ozao-Choy ◽

Ping Y. Pan ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Kinase Inhibitor ◽

Suppressor Cell ◽

The Novel ◽

T Regulatory Cell ◽

Regulatory Cell ◽

Treg Function ◽

Myeloid Derived Suppressor Cell

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307 Distinct Regulatory Dendritic Cell Subsets in Control of Treg Function in Acute Inflammation and Recovery from Colitis

Gastroenterology ◽

10.1016/s0016-5085(08)60210-3 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-43-A-44

Author(s):

Seiji Arihiro ◽

Bayasi Guleng ◽

Carmen Alonso Cotoner ◽

Jan H. Niess ◽

Sonal Gupta ◽

...

Keyword(s):

Dendritic Cell ◽

Acute Inflammation ◽

Treg Function ◽

Dendritic Cell Subsets

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Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures

Blood ◽

10.1182/blood-2009-01-199950 ◽

2009 ◽

Vol 113 (21) ◽

pp. 5125-5133 ◽

Cited By ~ 127

Author(s):

Dat Q. Tran ◽

John Andersson ◽

Donna Hardwick ◽

Lolita Bebris ◽

Gabor G. Illei ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Ex Vivo ◽

Magnetic Bead ◽

Receptor Type ◽

Type I ◽

Graft Versus Host ◽

Treg Function ◽

Health And Disease ◽

Unique Cell

Abstract Although adoptive transfer of regulatory T cells (Foxp3+ Tregs) has proven to be efficacious in the prevention and treatment of autoimmune diseases and graft-versus-host disease in rodents, a major obstacle for the use of Treg immunotherapy in humans is the difficulty of obtaining a highly purified preparation after ex vivo expansion. We have identified latency-associated peptide (LAP) and IL-1 receptor type I and II (CD121a/CD121b) as unique cell-surface markers that distinguish activated Tregs from activated FOXP3− and FOXP3+ non-Tregs. We show that it is feasible to sort expanded FOXP3+ Tregs from non-Tregs with the use of techniques for magnetic bead cell separation based on expression of these 3 markers. After separation, the final product contains greater than 90% fully functional FOXP3+ Tregs. This novel protocol should facilitate the purification of Tregs for both cell-based therapies as well as detailed studies of human Treg function in health and disease.

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Monocyte-Independent and -Dependent Regulation of Regulatory T-Cell Development in Mycoplasma Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa590 ◽

2020 ◽

Author(s):

Ryo Takahashi ◽

Tetsuo Shiohara ◽

Yoshiko Mizukawa

Keyword(s):

Th17 Cells ◽

Viral Infections ◽

T Cell Development ◽

Allergic Diseases ◽

Acute Stage ◽

Dependent Manner ◽

Virus Infections ◽

Treg Function ◽

Toll Like Receptor 2 ◽

And Function

Abstract Background Although Mycoplasma pneumoniae (MP) infection has been implicated in the pathogenesis of allergic diseases, the mechanism of this trigger remains unknown. We explored the mechanism for how MP infection could tilt the balance between regulatory T cells (Tregs) and Th17 cells. Methods We analyzed the frequency, phenotype, and function of Tregs in patients at the different stages of MP and various virus infections over a period of more than 1 year. We examined the effect of monocytes to elucidate signals that can regulate the balance between Treg and Th17 cells. Results The functional activity of Tregs was profoundly impaired during the acute stage of MP as well as viral infections. Upon resolution, however, the Treg function remained impaired even 1 year after MP infection. In the resolution stage, the impaired Treg function was associated with an increase in interleukin (IL) 17A+ Tregs and Th17 cells. Development of Th17 cells was dependent on the “aberrant” proinflammatory monocytes (pMOs), characterized by potent ability to produce IL-6 in a Toll-like receptor 2–dependent manner. Conclusions Depending on the prevalence of the pMOs, Tregs and Th17 cells could mutually regulate the number and function of the other. The pMOs/IL-6 could be crucial therapeutic targets against MP-induced allergic diseases.

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