T-reg

Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (Treg ) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections...

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that destroys insulin-producing pancreatic β-cells. Insulin replacement therapy is currently the mainstay of treatment for T1DM; however, treatment with insulin does not ameliorate disease progression, as dysregulated immune response and inflammation continue to cause further pancreatic β-cell degradation. Therefore, shifting therapeutic strategies toward immunomodulating approaches could be effective to prevent and reverse disease progression...

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression...

Breast cancer is the leading cause of cancer-related death in women worldwide. It is well known that breast cancer shows significant alterations in the tumor microenvironment (TME), which is composed of a variety of immune cells, including natural killer (NK) cells, that have a key role in tumor development or anti-tumor responses in breast cancer patients. Luminal B (BT474) and triple-negative breast cancer (HS578T) cell lines were cultured in 2D and 3D model systems. PMBCs from healthy donors were isolated and treated with extracellular vesicles (EVs) from monolayer and spheroids of BT474 and HS578T and analyzed using cytofluorimetric approaches...

In the quest for more precise and effective organ transplantation therapies, chimeric antigen receptor (CAR) regulatory T cell (Treg ) therapies represent a potential cutting-edge advance. This review comprehensively analyses CAR Tregs and how they may address important drawbacks of polyclonal Tregs and conventional immunosuppressants. We examine a growing body of preclinical findings of CAR Treg therapy in transplantation, discuss CAR Treg design specifics, and explore established and attractive new targets in transplantation...

Anti-CD38 antibody therapies have transformed multiple myeloma (MM) treatment. However, a large fraction of patients inevitably relapses. To understand this, we investigated 32 relapsed MM patients treated with daratumumab, lenalidomide, and dexamethasone (Dara-Rd; NCT03848676 ). Whole genome sequencing (WGS) before and after treatment pinpointed genomic drivers associated with early progression, including RPL5 loss and APOBEC mutagenesis. Flow cytometry on 202 blood samples, collected every three months until progression for 31 patients, revealed distinct immune changes significantly impacting clinical outcomes...

Regulatory T (Treg ) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell-targeted immunotherapy in mice, we find that CD4+ Foxp3- conventional T (Tconv ) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3- Tconv cells within tumors adopt a Treg cell-like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo...

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a frequently intervention for patients with locally advanced gastric cancer (GC). Nevertheless, its impact on the tumor immune microenvironment remains unclear. METHODS: We used immunohistochemistry to identify T-cell subpopulations, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) in the GC microenvironment (GCME) among paired samples (pre-chemotherapy and post-chemotherapy) from 48 NAC-treated patients...

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies for which graft-versus-host disease (GVHD) remains a major complication. The use of donor T regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation of an engineered graft product (T-reg graft) consisting of the timed, sequential infusion of CD34+ hematopoietic stem cells and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol remains unclear...

The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4+ T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (Treg ) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of Scd1-deficient mice...

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a promising alternative for the treatment of patients with allergic rhinitis, providing similar therapeutic efficacy to conventional allergen-specific immunotherapy (AIT). However, the allergic mechanism of ILIT is not completely known. AIM: The aim of this study was to determine the efficacy of ILIT in a house dust mite (HDM) mouse model of allergic rhinitis. METHODS: BALB/c mice were divided into four groups: G1, control without allergy; G2, allergy sensitized with HDM; G3, allergy with ILIT (starting with HDM 1...

Cardiac fibrosis remains an unmet clinical need that has so far proven difficult to eliminate using current therapies. As such, novel technologies are needed that can target the pathologic fibroblasts responsible for fibrosis and adverse tissue remodeling. mRNA encapsulated in lipid nanoparticles (LNPs) are an emerging technology that could offer a solution to this problem. Indeed, this strategy has already shown clinical success with the mRNA COVID-19 vaccines. In this AJP perspective, we discuss how this technology can be leveraged to specifically target cardiac fibrosis via several complementary strategies...

MHC-E restricted CD8+ regulatory T cells have a restricted TCR repertoire and eliminate pathogenic CD4 T cells to mediate immune responses.

In last decades a simultaneous increase in the prevalence of atopic and autoimmune disorders in pediatric population has been observed. Despite the Th1-Th2 paradigm, supporting the polarization of the immune system with Th1 response involved in autoimmune diseases and Th2 response leading to hypersensitivity reactions, recent evidence suggests a possible coexistence of common pathogenic pathways as result of shared immune dysregulation. Similar genes and other mechanisms such as epithelial barrier damage, gut microbiota dysbiosis and reduced number of T regs and IL-10 contribute to the onset of allergy and autoimmunity...

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No abstract text is available yet for this article.

This writing serves as a commentary on the findings presented in the original manuscript by Yang et al. in 2023, published in the Journal of Leukocyte Biology (JLB). This commentary first summarizes the spatial-temporal dynamics of regulatory T-cells (T-reg) derived from mice (Tabula Muris Senis) of different ages (3M, 18M, and 24M) at different anatomical niches like lymph nodes and bone marrow. We also reported possible combinations of receptor-ligand interactions among T follicular regulatory cells (Tfr), T follicular helper cells (Tfr), and Germinal Centre (GC) B-cells, such as Calmodulin/Fas axis and PSGL-1/L-selectin axis...

Type 2 diabetes mellitus (T2D) has become a global epidemic affecting the health of millions of people. T2D is a complex and multifactorial metabolic disease, largely characterized by a combination of impaired insulin secretion from β cells residing within the islets of the pancreas and peripheral insulin resistance. In this article, we discuss the current state and risk factors for T2D, conventional treatment options, and upcoming strategies, including progress in the areas of allogeneic and xenogeneic islet transplantation, with a major focus on stem cell-derived β cells and associated technologies...

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune polymorphous disease that primarily affects women of reproductive age. This gender disparity has suggested the importance of investigating the role of reproductive hormones in the pathogenesis of the disease. Estradiol, the most potent form of estrogen, plays a key role in shaping the immune system including the production of lymphocytes, the peripheral differentiation of regulatory T cells (T-regs), antibody production, and the complement and interferon systems, and has been studied in the pathogenesis of systemic lupus erythematosus (SLE)...

UNLABELLED: STING activation induces lymphocyte cell death that is independent of type I IFNs. The in vivo significance and mechanism of STING-mediated cell death is unclear. Using STING knock-in mice, we found that lymphocytes from the HAQ , AQ , and Q293 mice are resistant to STING-mediated cell death ex vivo , establishing a critical role of STING residue 293 in cell death. CD4 T cellpenia is evident in STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING mutations...