CD4+CD25+LAG3+ T Cells With a Feature of Th17 Cells Associated With Systemic Lupus Erythematosus Disease Activity

Kato, Rika; Sumitomo, Shuji; Tsuchida, Yoshiaki; Tsuchiya, Haruka; Nakachi, Shinichiro; Sakurai, Keiichi; Hanata, Norio; Nagafuchi, Yasuo; Kubo, Kanae; Tateishi, Shoko; Kanda, Hiroko; Okamura, Tomohisa; Yamamoto, Kazuhiko; Fujio, Keishi

doi:10.3389/fimmu.2019.01619

Cited by 22 publications

(15 citation statements)

References 53 publications

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“…Co-culture of iTregs with MSC feeder cells significantly improved the number and suppressive function of iTreg during 21 day IL-2 based ex vivo expansion. MSC co-culture increased iTreg expression of CD25, CTLA-4, and ICOS, while expression of LAG-3 and TIM-3, associated with exhaustion of activated T cells 56 – 62 , was decreased. We observed higher proportions of CD62L + and absolute numbers of CD45RA + iTreg cells after 21 day IL-2 expansion co-culture on MSC feeder cells.…”

Section: Discussionmentioning

confidence: 95%

Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability

Zwick

Kenyon

et al. 2021

Sci Rep

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The key obstacle to clinical application of human inducible regulatory T cells (iTreg) as an adoptive cell therapy in autoimmune disorders is loss of FOXP3 expression in an inflammatory milieu. Here we report human iTreg co-cultured with bone marrow-derived mesenchymal stromal cells (MSCs) during short-term ex vivo expansion enhances the stability of iTreg FOXP3 expression and suppressive function in vitro and in vivo, and further that a key mechanism of action is MSC mitochondrial (mt) transfer via tunneling nanotubules (TNT). MSC mt transfer is driven by mitochondrial metabolic function (CD39/CD73 signaling) in proliferating iTreg and promotes iTreg expression of FOXP3 stabilizing factors BACH2 and SENP3. These results elucidate cellular and molecular mechanisms underlying human MSC mt transfer to proliferating cells. MSC mt transfer stabilizes FOXP3 expression in iTregs, thereby enhancing and sustaining their suppressive function in inflammatory conditions in vitro and in vivo.

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Section: Discussionmentioning

confidence: 95%

Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability

Zwick

Kenyon

et al. 2021

Sci Rep

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“…IL-10 has been shown to restrict T cell proliferation by reducing the INF gamma and IL-2 synthesis, thereby inhibiting proliferative and cytokine responses in T cells [ 151 ]. IL-17 is reported to be secreted by the LAG-3 positive T cells [ 152 ] and IL-17 mRNA expression is positively correlated with LAG-3 T cells in gastric cancer [ 100 ]. Thus, patients with IL-17 overexpression may benefited more from the treatment of LAG-3 inhibitors.…”

Section: Influence Of Lifestyle On Outcome Of Cpimentioning

confidence: 99%

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Deshpande

Sharma

Watabe

2020

Cancers

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Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

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“…However, both B and T cells are, in turn, under the regulatory control of a subset of CD4+CD25+ T cells known as regulatory T cells (Tregs). 3,4 Naturally arising Tregs play a key role in the maintenance of homeostasis within the immune system by suppression of autoreactive T cells and therefore, deficiency of Tregs induces autoimmune diseases. 5 Tregs suppress the proliferation of naive T cells and their in vivo differentiation to effector T cells.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that T cells play an important role in the regulation of B‐cell activation. However, both B and T cells are, in turn, under the regulatory control of a subset of CD4+CD25+ T cells known as regulatory T cells (Tregs) 3,4 …”

Section: Introductionmentioning

confidence: 99%

Functional inhibition of regulatory CD4+CD25+T cells in peripheral blood of patients with pemphigus vulgaris

Su¹,

Zhou²,

Ke³

et al. 2020

Clin. Exp. Dermatol.

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Summary Background Pemphigus vulgaris (PV) is a potentially life‐threatening autoimmune bullous disease affecting the skin and mucous membranes. Its pathogenic mechanism is still not fully understood. Regulatory T cells (Tregs) have been reported to play a significant role in regulating immune homeostasis in autoimmune disorders, such as PV. Aim To investigate the potential role of Tregs in the immunopathogenesis of PV. Methods We enrolled 15 patients with PV and 15 healthy controls (HCs). Peripheral blood samples were collected from all participants before treatment. This was followed by flow cytometric, real‐time reverse transcription PCR, and in vitro inhibition‐based functional assays to explore the immunopathogenesis of Tregs in PV. Results Our results showed no statistically significant differences in total CD4+CD25+ cells and CD4+CD25high cells. In addition, expression levels of FOXP3 mRNA and the corresponding FOXP3 protein remained unchanged in the patients with PV and the HCs. However, the in vitro suppressive activity of CD4+CD25+ T cells was impaired in patients with PV compared with HCs. Conclusions Our observations suggest that inhibition of suppressive activity of Treg cells may be involved in the pathogenesis of PV.

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CD4+CD25+LAG3+ T Cells With a Feature of Th17 Cells Associated With Systemic Lupus Erythematosus Disease Activity

Cited by 22 publications

References 53 publications

Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability

Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Functional inhibition of regulatory CD4+CD25+T cells in peripheral blood of patients with pemphigus vulgaris

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