Increased levels of pathogenic Th17 cells and diminished function of CD69+ Treg lymphocytes in patients with overweight

Mendoza-Pérez, Alejandra; Vitales-Noyola, Marlen; González-Baranda, Larisa; Álvarez-Quiroga, Crisol; Hernández-Castro, Berenice; Monsiváis‐Urenda, Adriana; Baranda, Lourdes; Niño-Moreno, Perla; Hurtado, Gilberto; Sánchez-Gutiérrez, Raquel; González‐Amaro, Roberto

doi:10.1093/cei/uxac051

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…The proportion of Tregs rose from 0.79% in NG to 2.48% in HG, and they highly expressed the level of CD69 . As we know, CD69+Tregs play a critical role in the maintenance of immunologic tolerance and suppression of innate immune responses ( 41 ). We also found higher proportions of two subclusters (CD4 TCM and CD8 TCM) with high expression of GATA3 that contributed to the maintenance of immune activity ( 42 ) under high stress.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Wang

Long

et al. 2023

Front. Immunol.

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IntroductionHigh stress in the compartment surrounded by the deep fascia can cause acute compartment syndrome (ACS) that may result in necrosis of the limbs. The study aims to investigate the cellular heterogeneity of the deep fascia in ACS patients by single-cell RNA sequencing (scRNA-seq).MethodsWe collected deep fascia samples from patients with ACS (high-stress group, HG, n=3) and patients receiving thigh amputation due to osteosarcoma (normal-stress group, NG, n=3). We utilized ultrasound and scanning electron microscopy to observe the morphologic change of the deep fascia, used multiplex staining and multispectral imaging to explore immune cell infiltration, and applied scRNA-seq to investigate the cellular heterogeneity of the deep fascia and to identify differentially expressed genes.ResultsNotably, we identified GZMK+interferon-act CD4 central memory T cells as a specific high-stress compartment subcluster expressing interferon-related genes. Additionally, the changes in the proportions of inflammation-related subclusters, such as the increased proportion of M2 macrophages and decreased proportion of M1 macrophages, may play crucial roles in the balance of pro-inflammatory and anti-inflammatory in the development of ACS. Furthermore, we found that heat shock protein genes were highly expressed but metal ion-related genes (S100 family and metallothionein family) were down-regulated in various subpopulations under high stress.ConclusionsWe identified a high stress-specific subcluster and variations in immune cells and fibroblast subclusters, as well as their differentially expressed genes, in ACS patients. Our findings reveal the functions of the deep fascia in the pathophysiology of ACS, providing new approaches for its treatment and prevention.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Wang

Long

et al. 2023

Front. Immunol.

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“…As in the case of Treg cells, several studies have shown abnormal levels of Th17 cells in the peripheral blood from patients with T2DM [ 38 ]. Both increased and normal levels of CD4 + IL-17 + lymphocytes have been detected in these patients [ 16 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus

Knott-Torcal,

de la Blanca,

Serrano-Somavilla

et al. 2024

J Endocrinol Invest

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Background Type 2 diabetes mellitus (T2DM) is usually accompanied by a low-grade inflammatory phenomenon, which participates in the pathogenesis of different complications of this condition. The inflammatory response is under the regulation of different mechanisms, including T regulatory (Treg) lymphocytes. However, the possible role of type 1 T regulatory (Tr1) cells in T2DM has not been explored so far. Aim To carry out a quantitative analysis of Tr1 lymphocytes and other immune cell subsets in patients with T2DM and correlate these results with clinical findings and treatments. Materials and methods Sixty patients with T2DM and twenty-three healthy controls were included in the study. Biochemical and anthropometric variables were evaluated, and Tr1 lymphocytes (CD4+CD49+LAG-3+IL-10+) and other cell subsets (Th17, Th22 and Foxp3 + Treg cells) were analyzed in peripheral blood samples by multiparametric flow cytometry. Results Significant increased levels of Tr1 cells were detected in patients with severe and mild disease, compared to healthy controls. In addition, CD4+IL-10+ lymphocytes were also increased in patients with T2DM. In contrast, similar levels of Foxp3+ Treg cells, Th17 and Th22 lymphocytes were observed in patients and controls. Likewise, no significant associations were detected between Tr1 cell levels and different clinical and laboratory parameters. However, those patients receiving glucagon-like peptide-1 receptor agonists (GLP-1-RA) showed similar levels of Tr1 cells than healthy controls, and significant lower numbers than untreated patients. Conclusion We observed an increase in Tr1 and CD4+IL10+ lymphocyte levels in T2DM. Moreover, GLP1-RA treatment was significantly associated with normalization of the Tr1 levels. This highlights another potential immune dysfunction in patients with T2DM, which could participate in the pathogenesis of this condition.

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“…12 In a recent experimental study, an increase of Th17 cells and a reduction of CD69+ regulatory T cells (T reg) were demonstrated in people with metabolic dysfunction showing dyslipidemia and insulin resistance. 13 The number of pathogenic Th17 cells was mainly increased in people that were also overweight.…”

Section: Comor Bidit Y I N Psor I Atic Dise Asementioning

confidence: 99%

Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation

Mrowietz

Sümbül

Gerdes

2023

Acad Dermatol Venereol

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Psoriatic disease is a chronic, systemic immune‐mediated inflammatory disorder comprising three major domains, skin, vascular and bone/joint inflammation. It is known for a long time that psoriatic disease is associated with a number of conditions such as hypertension, dyslipidemia, diabetes (metabolic syndrome) and depression. Up to one out of five people with psoriasis show concomitant depression. In the past, this was attributed to psychological stress of suffering from a chronic condition that is often visible and itchy, leading to stigmatization and adding to a significant burden of disease. Recent data provide evidence that depression associated with psoriatic disease is linked to the specific inflammatory pattern with IL‐23, IL‐17 family cytokines, TNF, IL‐6 and IL‐8 causing neuroinflammation and subsequently depression or depressive behaviour and/or anxiety. Psoriatic disease shows a distinct pattern of immune cells (e.g. dendritic cells, Th17 cells, neutrophils), mediators (e.g. IL‐17A/F, IL‐23, TNF) and tissue‐related factors in all major domains that is different from other inflammatory dermatoses. There is a striking similarity between the inflammatory pattern in psoriatic disease and neuroinflammation that leads to depression. A number of risk factors have been identified in psoriatic disease, the most important of which are obesity and tobacco smoking. Obesity is known as a major risk factor for depression and anxiety due to its inflammatory signature. Apart from psychotherapy and anti‐depressive medication, targeted treatments for psoriasis, including TNF, IL‐17 and IL‐23 inhibitors, can improve depression/depressive symptoms. The review summarizes the current knowledge about depression as a comorbidity in psoriatic disease.

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Increased levels of pathogenic Th17 cells and diminished function of CD69+ Treg lymphocytes in patients with overweight

Cited by 4 publications

References 31 publications

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus

Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation

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