Adenovirus-mediated interleukin-35 gene transfer suppresses allergic airway inflammation in a murine model of asthma

Abstract

These results demonstrate that adenovirus-mediated delivery of interleukin-35 gene can mitigate allergic airway inflammation in experimental asthma and suggest that IL-35 may offer a novel therapeutic approach to treat allergic asthma.

Regulatory cytokine function in the respiratory tract

“…163 Similar results were obtained where IL-35 was expressed in the airways using an adenoviral vector, throughout a model of peripheral sensitization and airway challenge with ovalbumin, concomitant with suppression of IL-17A production and increased numbers of pulmonary FoxP3 + Tregs. 164 Although these studies demonstrate the capacity for local IL-35 to dampen allergic inflammation in the lung, further work will be required to determine the importance of endogenous IL-35 in this context. In a model of AAD elicited by airway sensitization to ovalbumin using LPS as an adjuvant, which drives a Th17-dominated disease to which mice become tolerant following repeated airway ovalbumin exposures, tolerance was dependent upon expansion of a population of ICOS + FoxP3 + Tregs.…”

Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis

“…Dong et al 9 showed that intraperitoneal injection of rIL-35 reduced eosinophil counts in BALF. Li et al 10 showed that intranasal administration of adenovirus expressing IL-35 reduced the numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in BALF. These findings suggest that intratracheal, intramuscular, intraperitoneal, or intranasal administration of IL-35 may attenuate asthma.…”

“…Dong et al 9 also reported that administration of recombinant fusion protein of murine IL- 35 and human Fc fragment (rIL-35) reduced eosinophil counts in BALF. Li et al 10 documented a reduction in the numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in BALF with administration of adenovirus expressing IL-35. These findings suggest that IL-35 can attenuate asthma.…”

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrosis

“…This newly identified member of the heterodimeric IL-12 family has the capacity to suppress inflammation and immune responses (14,15). IL-35 was reported to play a vital anti-inflammatory role in protecting against several inflammatory and autoimmune diseases including inflammatory bowel disease, chronic intestinal inflammation, rheumatoid arthritis, and asthma (16,17,18,19). Mechanistically, IL-35 first interacts with its receptor (IL-35R), which is composed of three different dimers of IL-12Rβ2 and GP130, namely GP130-IL-12Rβ2, GP130-GP130, or IL-12Rβ2-IL-12Rβ2.…”