Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis DOI Creative Commons

Peizhi Tao,

Beiting Su,

Xueyan Mao

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103594 - 103594

Published: March 13, 2025

Cigarette smoke (CS) exposure amplifies neutrophil accumulation. IL-35, a novel cytokine with anti-inflammatory properties, is involved in protection against asthma. However, the biological roles of neutrophils and precise molecular mechanisms IL-35 CS exposed-asthma remain unclear. We showed that exacerbation leads to dramatically increased counts an imbalance DC-Th17/Treg immune responses. RNA sequencing revealed NETs, part key process neutrophils, were significantly upregulated context treatment downregulated NET-associated gene expression. Targeted degradation rather than depletion, alleviated exposed-asthma. Mechanistically, STAT3 phosphorylation promoted ferroptosis, exacerbating NET release, which turn enhanced dendritic cell (DC) antigen presentation, activated T cells, specifically Th17 differentiation while inhibiting Treg cells. acting on gp130 receptor STAT3-mediated ferroptosis-associated formation. In summary, our study mechanism by inhibited formation, subsequently alleviating neutrophilic inflammation restoring exposed-asthma, highlighting potential as targeted therapeutic strategy.

Language: Английский

T Cell Exhaustion DOI
Andrew Baessler, Dario A.A. Vignali

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 179 - 206

Published: Jan. 2, 2024

T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage healthy cells preventing autoimmunity. exhaustion serves as a regulatory mechanism limit the activity effector function undergoing chronic antigen stimulation. Exhausted exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, metabolism; and, most importantly, reduced function. While helps restrain caused by aberrant in settings autoimmune disease, it limits ability respond persistent infection cancer, leading disease progression. Here we review process exhaustion, detailing key characteristics drivers well highlighting our current understanding underlying transcriptional epigenetic programming. We discuss how can targeted enhance functionality cancer.

Language: Английский

Citations

75
Diabetic complications and prospective immunotherapy DOI Creative Commons

Lewis Reynolds,

Zhengkang Luo, K. N. Singh

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

The incidence of Diabetes Mellitus is increasing globally. Individuals who have been burdened with diabetes for many years often develop complications as a result hyperglycemia. More and more research being conducted highlighting inflammation an important factor in disease progression. In all kinds diabetes, hyperglycemia leads to activation alternative glucose metabolic pathways, resulting problematic by-products including reactive oxygen species advanced glycation end products. This review takes look into the pathogenesis three specific diabetic complications; retinopathy, nephropathy neuropathy well their current treatment options. By considering recent papers investigating effects immunotherapy on relevant conditions animal models, multiple strategies are suggested future prevention emphasis molecular targets associated inflammation.

Language: Английский

Citations

23
Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions DOI Creative Commons
Karen Hildenbrand, Sina Bohnacker, Priyanka Rajeev Menon

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(43)

Published: Oct. 25, 2023

Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each member consists of an α β subunit together form composite cytokine. Within IL-12 family, IL-35 remains particularly ill-characterized on molecular level despite its key role autoimmune diseases cancer. Here we show both subunits, IL-12α EBI3, mutually promote their secretion from cells but not necessarily as heterodimer. Our data demonstrate EBI3 stable isolation act anti-inflammatory molecules. Both reduce proinflammatory cytokines induce development regulatory T cells. Together, our study reveals subunits IL-35, to be functionally active molecules own. This extends understanding human cytokine repertoire basis for immunotherapeutic approaches.

Language: Английский

Citations

15
Regulatory T cell-based therapy in type 1 diabetes: Latest breakthroughs and evidence DOI

Qiongxiao Huang,

Jing Zhu

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112724 - 112724

Published: Aug. 3, 2024

Language: Английский

Citations

6
Harnessing the biology of regulatory T cells to treat disease DOI
Christine M. Wardell, Dominic A. Boardman, Megan K. Levings

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Language: Английский

Citations

5
Biogenesis and engineering of interleukin 12 family cytokines DOI Creative Commons
Karen Hildenbrand,

Isabel Aschenbrenner,

Fabian Christoph Franke

et al.

Trends in Biochemical Sciences, Journal Year: 2022, Volume and Issue: 47(11), P. 936 - 949

Published: June 10, 2022

Language: Английский

Citations

20
Dysregulation of T cell response in the pathogenesis of inflammatory bowel disease DOI Open Access

Rucha Chandwaskar,

Rajdeep Dalal,

Saurabh Gupta

et al.

Scandinavian Journal of Immunology, Journal Year: 2024, Volume and Issue: 100(6)

Published: Oct. 12, 2024

Inflammatory bowel disease (IBD), comprised of Crohn's (CD) and ulcerative colitis (UC), are gut inflammatory diseases that were earlier prevalent in the Western Hemisphere but now on rise East, with India standing second highest incidence rate world. Inflammation IBD is a cause dysregulated immune response, wherein helper T (Th) cell subsets their cytokines play major role pathogenesis IBD. In addition, microbiota, environmental factors such as dietary host genetics influence outcome severity Dysregulation between effector regulatory cells drives inflammation, like Th1, Th17 Th9 Th lineages found to be increased patients. this review, we attempted discuss different together other CD8

Language: Английский

Citations

5
Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia DOI Open Access
Nour Sabiha Naji,

Mrudula Sathish,

Theodoros Karantanos

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3974 - 3974

Published: Nov. 27, 2024

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML affect survival outcomes. The dysregulation cytokine network may foster pro-tumorigenic microenvironment, increasing leukemic cell proliferation, decreasing driving drug resistance. dominance pro-inflammatory mediators such as IL-11β, TNF-α IL-6 over anti-inflammatory TGF-β IL-10 has been implicated tumor progression. Additionally, cytokines have favored certain populations hematopoietic stem progenitor cells with mutated clonal hematopoiesis genes. This article summarizes current knowledge about pathways AML, their modes action implications for immune tolerance hematopoiesis, aim finding potential therapeutic interventions to improve clinical outcomes patients.

Language: Английский

Citations

5
The Current and Future of Biomarkers of Immune Related Adverse Events DOI

William Bracamonte‐Baran,

Sang T. Kim

Rheumatic Disease Clinics of North America, Journal Year: 2024, Volume and Issue: 50(2), P. 201 - 227

Published: March 12, 2024

Language: Английский

Citations

4
FOXP3, IL-35, and PD-L1 in intra- and peritumoral lymphocytic infiltrate of cutaneous melanomas as an important part of antitumor immunity DOI Creative Commons
Vladimír Židlík, Pavel Hurník, Yvetta Vantuchová

et al.

Biomedical Papers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Background. The tumor microenvironment is a significant mediator enabling growth and progression. Tumor-infiltrating lymphocytes (TILs) are an important component of this but cells develop mechanisms by which they can escape the action immune system. Immunosuppressive cooperate with each other involve system, itself, chemokines cytokines. In study, we examined FOXP3+, IL-35+, PD-L1+ in tissues as contributing to immunosuppression some tumors, including melanoma. Such also associated progression, early metastasis, prognosis. Methods Results. 95 cutaneous melanomas 25 melanocytic nevi control group were immunohistochemistry for lymphocytes. Melanomas divided into four groups according TNM classification: pT1 (35), pT2 (21), pT3 pT4 (18). enriched pT3- pT4-stage melanomas, especially periphery lesions (P<0.001). number FOXP3+ was positively correlated stage disease, center tumors Likewise, IL-35+ (P<0.001) tumor. Conclusion. This article demonstrates that immunosuppressive environment develops proportion most changes found at periphery, confirming heterogeneity stroma more pronounced advanced may contribute greater aggressiveness these peripheral zones.

Language: Английский

Citations

0