Different expression levels of interleukin-35 in asthma phenotypes

Abstract

Background: Interleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes. Objective: We aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes. Methods: Sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively. Results: Sputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/ mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors. Conclusions: Sputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.

IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

“…Prior studies have explored the interactions between IL-35 and other intratumoral immune cell populations not discussed above, such as neutrophils, MDSCs, and NK cells (88)(89)(90), although more research on these interactions is warranted. Antitumorigenic N1 neutrophils and pro-tumorigenic N2 neutrophils are two different subsets of neutrophils identified in previous studies (91).…”

The Role of IL-35 in the Pathophysiological Processes of Liver Disease

“…Generally, hepatitis B virus (HBV) and hepatitis C virus (HCV) were common in liver injury, both of which were non-cytopathic virus ( Gonzalez and Gordon, 2020 ; Spyrou et al, 2020 ). It has been reported that IL-35 was associated with significant inflammation inhibition, which can inhibit the proliferation of T cell and the function f its effector ( Li et al, 2020a ). This compelling function pushed us to figure out the theoretical basis and other beneficial effects of IL-35 in the immune-pathogenesis of HBV, HCV hepatitis, and autoimmune hepatitis (AIH).…”

IL-35 inhibits cell pyroptosis and attenuates cell injury in TNF-α-induced bronchial epithelial cells via p38 MAPK signaling pathway

“…Notably, due to an increase of TNF-α mRNA and protein expression in the airways of asthmatic patients, it was raised the possibility of TNF-α participating in the dysregulation of the inflammatory response in the asthmatic airways [ 11 ]. Meanwhile, the study found that IL-35 participated in the pathogenesis of asthma some inflammatory and autoimmune diseases, including asthma, by brokering the inhibition of effector T cells [ 6 , 12 ]. However, studies regarding the role of IL-35 on cell pyroptosis and often occurring in inflammatory diseases are not yet clarified.…”