T‑regulatory cells from patients with rheumatoid arthritis retain suppressor functions <i>in vitro</i>

Shevyrev, Daniil; Tereshchenko, Valeriy; Козлов, В. А.; Сизиков, А. Э.; Чумасова, О. А.; Koksharova, V.

doi:10.3892/etm.2021.9641

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…These data suggest a constant number of T cells that are exTregs. However, the conversion of exTregs into T H 17 cells (exTreg-T H 17 cells) was almost non-existent under normoxia, similar to the findings of other studies (Komatsu et al, 2014;Basdeo et al, 2015;Shevyrev et al, 2021); however, exTreg-T H 17 cells were prevalent under hypoxia, demonstrating a hypoxiadependent mechanism of phenotypic conversion or differentiation.…”

Section: Discussionsupporting

confidence: 88%

“…FoxP3 is the major transcription factor found in Tregs. This phenotype has been identified in Tregs collected from the peripheral blood of rheumatoid arthritis patients in a disease severity-dependent manner ( Komatsu et al, 2014 ; Go et al, 2021 ; Shevyrev et al, 2021 ). When looking at OX40, Tregs with elevated levels of OX40 were found to have a less suppressive capacity through the downregulation of IL-10, one of the major anti-inflammatory cytokines released by Tregs ( So and Croft, 2007 ; Fu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Chronic hypoxia disrupts T regulatory cell phenotype contributing to the emergence of exTreg-TH17 cells

Lantz,

Moriwaki,

Oyebamiji

et al. 2024

Front. Physiol.

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The imbalance between pro-inflammatory T helper 17 (TH17) cells and anti-inflammatory regulatory T cells (Tregs) has been implicated in multiple inflammatory and autoimmune conditions, but the effects of chronic hypoxia (CH) on this balance have yet to be explored. CH-exposed mice have an increased prevalence of TH17 cells in the lungs with no change in Tregs. This imbalance is significant because it precedes the development of pulmonary hypertension (PH), and TH17 cells are a major contributor to CH-induced PH. While Tregs have been shown to attenuate or prevent the development of certain types of PH through activation and adoptive transfer experiments, why Tregs remain unable to prevent disease progression naturally, specifically in CH-induced PH, remains unclear. Our study aimed to test the hypothesis that increased TH17 cells observed following CH are caused by decreased circulating levels of Tregs and switching of Tregs to exTreg-TH17 cells, following CH. We compared gene expression profiles of Tregs from normoxia or 5-day CH splenocytes harvested from Foxp3tm9(EGFP/cre/ERT2)Ayr/J x Ai14-tdTomato mice, which allowed for Treg lineage tracing through the presence or absence of EGFP and/or tdTomato expression. We found Tregs in CH exposed mice contained gene profiles consistent with decreased suppressive ability. We determined cell prevalence and expression of CD25 and OX40, proteins critical for Treg function, in splenocytes from Foxp3tm9(EGFP/cre/ERT2)Ayr/J x Ai14-tdTomato mice under the same conditions. We found TH17 cells to be increased and Tregs to be decreased, following CH, with protein expression of CD25 and OX40 in Tregs matching the gene expression data. Finally, using the lineage tracing ability of this mouse model, we were able to demonstrate the emergence of exTreg-TH17 cells, following CH. These findings suggest that CH causes a decrease in Treg suppressive capacity, and exTregs respond to CH by transitioning to TH17 cells, both of which tilt the Treg–TH17 cell balance toward TH17 cells, creating a pro-inflammatory environment.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Chronic hypoxia disrupts T regulatory cell phenotype contributing to the emergence of exTreg-TH17 cells

Lantz,

Moriwaki,

Oyebamiji

et al. 2024

Front. Physiol.

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“…In some cases, such transitions of Ag-specific clones between subpopulations of T cells are involved in pathological processes. For example, an important role of a transition Treg ↔ Th17 was established in patients with different autoimmune conditions, graft rejection, and oncologic processes (58)(59)(60)(61)(62)(63). Besides, plasticity Th17 !…”

Section: Organization Of the Human T-cell Repertoirementioning

confidence: 99%

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

2021

Self Cite

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In this review, we described the structure and organization of antigen-recognizing repertoires of B and T cells from the standpoint of modern immunology. We summarized the latest advances in bioinformatics analysis of sequencing data from T and B cell repertoires and also presented contemporary ideas about the mechanisms of clonal diversity formation at different stages of organism development. At the same time, we focused on the importance of the allelic variants of the HLA genes and spectra of presented antigens for the formation of T-cell receptors (TCR) landscapes. The main idea of this review is that immune equilibrium and proper functioning of immunity are highly dependent on the interaction between the recognition and the presentation landscapes of antigens. Certain changes in these landscapes can occur during life, which can affect the protective function of adaptive immunity. We described some mechanisms associated with these changes, for example, the conversion of effector cells into regulatory cells and vice versa due to the trans-differentiation or bystander effect, changes in the clonal organization of the general TCR repertoire due to homeostatic proliferation or aging, and the background for the altered presentation of some antigens due to SNP mutations of MHC, or the alteration of the presenting antigens due to post-translational modifications. The authors suggest that such alterations can lead to an increase in the risk of the development of oncological and autoimmune diseases and influence the sensitivity of the organism to different infectious agents.

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“…Since Th17 cells have been reported to be plastic in terms of their capacity of acquiring features associated with other Th phenotypes, such as those related to Th1 cells or Tregs, the implications of our findings could relate to HO-1 expression in DCs, conferring these cells to have the ability to fine-tune Th responses with favorable outcomes regarding HSV infection [ 70 , 71 ]. Interestingly, we observed mixed populations of T cells including CD4 + T cells that were both RORγt- and FoxP3-positive, which has been related to a trans-differentiation state between Tregs and Th17 cells [ 49 , 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

et al. 2023

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Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1.

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T‑regulatory cells from patients with rheumatoid arthritis retain suppressor functions in vitro

Cited by 7 publications

References 48 publications

Chronic hypoxia disrupts T regulatory cell phenotype contributing to the emergence of exTreg-TH17 cells

Chronic hypoxia disrupts T regulatory cell phenotype contributing to the emergence of exTreg-TH17 cells

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

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