IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1β and IL-6. IL-1β stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464885 | PMC |
http://dx.doi.org/10.18632/oncotarget.16819 | DOI Listing |
Medicine (Baltimore)
November 2024
Pneumology Department, Baoding People's Hospital, Baoding, Hebei, China.
This study examines the diagnostic utility of the combined interleukin-33 (IL-33), interferon-γ (IFN-γ), and interleukin-35 (IL-35) test in tuberculous pleural effusion. Forty patients with pleural effusion of unknown etiology admitted to the hospital between December 2020 and December 2023 were selected as the study group. The patients were further categorized into tuberculous (TB) (n = 20) and malignant (n = 20) groups on the basis of their relevant data, while sera from 20 healthy medical checkups were used as control group.
View Article and Find Full Text PDFViruses
December 2024
Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA.
View Article and Find Full Text PDFMedicina (Kaunas)
November 2024
Department of Internal Medicine and Nephrology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic renal disease with a complex physiopathology. More and more studies sustain that inflammation plays a crucial role in ADPKD pathogenesis and progression. We evaluated IL-12 involvement in ADPKD pathophysiology by assessing the serum levels of its monomers and heterodimers.
View Article and Find Full Text PDFJ Transl Autoimmun
June 2025
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
In recent years, the discovery of IL-12 family cytokines, which includes IL-12, IL-23, IL-27, IL-35, and IL-39, whose biological functions directly or indirectly affect various autoimmune diseases. In autoimmune diseases, IL-12 family cytokines are aberrantly expressed to varying degrees. These cytokines utilize shared subunits to influence T-cell activation and differentiation, thereby regulating the balance of T-cell subsets, which profoundly impacts the onset and progression of autoimmune diseases.
View Article and Find Full Text PDFAm J Pathol
December 2024
Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Periodontitis was reported to be associated with aspiration pneumonia. However, the relationship between periodontitis and aspiration pneumonia remains unclear. This study investigated the virulence factor of Porphyromonas gingivalis, which exacerbates aspiration pneumonia, and the role of IL-35, an inhibitory heterodimeric cytokine of EBI3 and p35, in aspiration pneumonia using Ebi3 knockout (KO) mice.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!