Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function

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Mitochondrial Oxidative Phosphorylation Regulates the Fate Decision between Pathogenic Th17 and Regulatory T Cells

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Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function

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CD4+CD25+调节性T细胞与人类获得性免疫缺陷病毒感染

CD4 CD25 是调节性T细胞中功能最重要的一类.它是一类具有特殊免疫调节功能的T细胞亚群.它能够抑制自身免疫病的发生和发展,参与肿瘤免疫的调节,同时在感染和移植免疫中也发挥着极其重要的作用.T细胞的这一亚群具有免疫调节和免疫抑制的特性,新近发现它亦与爱滋病的发生、发展关系密切.HIV进入人体后,CD4 CD25 调节性T细胞抑制了机体的免疫效应但它也同时被感染,最终由于细胞毒的作用而死亡.由于调节性T细胞数量的减少不能有效的发挥其抑制作用,HIV持续的过度活化使得T细胞逐渐耗竭说明在HIV发生、发展的不同阶段Treg细胞可能都发挥了免疫抑制作用,但是却对HIV感染与爱滋病发病的进程产生了不同的效应.此外,CD4 CD25 调节性T细胞还与HIV病毒的持续存在密切相关.本文就CD4 CD25 调节性T细胞与人类获得性免疫缺陷病毒(HIV)感染之间关系进行初步的探讨.     

Roles of Hopx in the differentiation and functions of immune cells

Homeodomain only protein (Hopx, HOPX) is a highly evolutionarily conserved, homeodomain-containing, small protein expressed in multiple tissues and cell types, including those of hematopoietic origin. The quasi-ubiquitous presence of Hopx contrasts with its specialized and context-dependent roles in various cell lineages. Recently, versatile functions of Hopx have been revealed in immune cells, including T lymphocytes with effector and regulatory roles. The induction of Hopx expression can indicate early developmental and differentiation pathways, and early Hopx expression characterizes the recently identified pre-effector T cells that become destined for subsequent effector differentiation. Further, specific molecular mechanisms of Hopx are indispensable for the functional homeostasis of peripherally induced regulatory T cells (pTreg cells). Here we offer a perspective on these diverse roles of Hopx in immune cells and discuss the recent advances that helped to clarify the relevant functions and mechanisms of Hopx.     

New insights into CD4+ T cell abnormalities in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by vasculopathy and excessive deposition of extracellular matrix, which causes fibrosis of the skin and internal organs and eventually leads to multiorgan dysfunction. Studies have shown that CD4⁺ T cell activation is a key factor in the pathogenesis of scleroderma because activated T cells can release various cytokines, resulting in inflammation, microvascular damage and fibrosis. T helper cell 17 (Th17) and regulatory T (Treg) cell activities are a hallmark SSc, as Th17-type cytokines can induce both inflammation and fibrosis. More recently, several studies have reported new T cell subsets, including Th9 and Th22 cells, along with their respective cytokines in the peripheral blood, serum and skin lesions of individuals with SSc. Herein, we review recent data on various CD4⁺ T helper cell subsets in SSc, and discuss potential roles of these cells in promoting inflammation and fibrosis.     

Modulation of immune response to induced‐arthritis by low‐level laser therapy

As low‐level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low‐level laser therapy (LLLT) on arthritis‐induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm^?2; LLLT at 30 Jcm^?2. Cytokine measurements by enzyme‐linked immunosorbent assay and mRNA cytokine relative levels by real‐time quantitative polymerase chain reaction were performed with arthritic ankle (IL‐1β, IL‐6, TNF‐α, IL‐10 and TGF‐β). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4⁺, CD8⁺, Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4⁺ and TCD8⁺ population enrichment were observed in LLLT at 3 and 30 Jcm^?2 groups, respectively. Furthermore, Treg TCD8⁺ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm^?2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation.      

TLR4-dependent effects of ISAg treatment on conventional T cell polarization in vivo

We recently demonstrated that the polysaccharide component of the Korean medicinal herb Angelica gigas (immuno-stimulatory fraction of A. gigas; ISAg) induces anticancer effects in mice by activating natural killer (NK) and natural killer T (NKT) cells. However, it is unclear whether the use of ISAg in vivo can affect the differentiation of conventional T cells. Here, we investigated the effects of ISAg on the activation of conventional CD4⁺ and CD8⁺ T cells. We found that the administration of ISAg induced the polarization of CD4⁺ T cells toward the acquisition of the Th1 phenotype in vivo. Additionally, in mice treated with ISAg, CD8⁺ T cells produced more IFNγ than in control mice treated with PBS. Moreover, treatment with ISAg activated CD4⁺ and CD8⁺ T cells as well as NK and NKT cells, resulting in the secretion of Th1-type cytokines in a toll-like receptor 4 (TLR4)-dependent manner, implying that TLR4 is critical for an optimal Th1 response. Interestingly, ISAg treatment increased the number of Foxp3⁺ Treg cells, but not of Th2 cells, compared to control mice treated with PBS, indicating that ISAg possesses an immunomodulatory capacity that can control adaptive immune responses. Taken together, our results indicate that ISAg possesses a Th1-enhancing activity that could be used to treat Th2-mediated allergic immune diseases such as atopic dermatitis.     

Adenosine A2B receptor antagonist suppresses differentiation to regulatory T cells without suppressing activation of T cells

Extracellular adenosine activates P1 receptors (A₁, A_2A, A_2B, A₃) on cellular membranes. Here, we investigated the involvement of P1 receptor-mediated signaling in differentiation to regulatory T cells (Treg). Treg were induced in vitro by incubating isolated CD4⁺CD62L⁺ naïve murine T cells under Treg-skewing conditions. Antagonists of A₁ and A_2B receptors suppressed the expression of Foxp3, a specific marker of Treg, and the production of IL-10, suggesting the involvement of A₁ and A_2B receptors in differentiation to Treg. We also investigated the effect of these antagonists on T cell activation, which is essential for differentiation to Treg, and found that A₁ antagonist, but not A_2B antagonist, suppressed T cell activation. We conclude that A₁ and A_2B receptors are both involved in differentiation to Treg, but through different mechanisms. Since A_2B antagonist blocked differentiation to Treg without suppressing T cell activation, it is possible that blockade of A_2B receptor would facilitate tumor immunity.