E3 ligase RNF128 plays a significant role in regulating type 2 immune responses by controlling the activation of group 2 innate lymphoid cells (ILC2s) during allergic inflammation triggered by Alternaria alternata.
Allergic lung inflammation, such as asthma, is characterized by the body's hyperactive response to inhaled allergens. One of the main drivers of this condition is the action of ILC2s, which release type 2 cytokines including IL-5 and IL-13, contributing to airway hyperreactivity and inflammation. Recent research has focused on the E3 ligase RNF128, known for its regulatory role over Th2 cells, but its impact on ILC2s had not been thoroughly explored until now.
Researchers from Jiangxi University of Traditional Chinese Medicine investigated the role of RNF128 using genetically modified mice lacking the RNF128 gene. They discovered significant findings: RNF128 was more highly expressed in lung ILC2s than in other immune cells, indicating its potential to modulate ILC2 function.
To assess the effects of RNF128 deficiency, the team exposed both RNF128-deficient and wild-type mice to A. alternata, which is well-known for inducing allergic reactions. They observed markedly increased numbers of eosinophils and higher levels of IL-5 and IL-13 cytokines in the bronchoalveolar lavage fluid of RNF128-deficient mice compared to their wild-type counterparts. This suggests RNF128 plays an inhibitory role in ILC2 activation and subsequent allergic inflammation.
Notably, the researchers found RNF128 deficiency promoted the expression of the interleukin-33 (IL-33) receptor ST2 on lung ILC2s. IL-33 is known to be the most potent factor for ILC2 activation, and its upregulation indicates how RNF128 normally acts to restrict excessive immune responses and prevent exaggerated allergic reactions.
The methods employed included flow cytometric analysis to quantify ILC2 populations and their cytokine production following allergen exposure. Through these methodologies, the study illustrated the direct influence of RNF128 on ILC2 development and function.
Overall, the findings from this study heighten our comprehension of the molecular mechanisms underpinning allergic lung inflammation and highlight the potential of targeting RNF128 as a novel therapeutic approach for treating allergic diseases such as asthma. Armed with this knowledge, researchers can explore new strategies to curb ILC2-mediated inflammation and associated pathologies.
The researchers concluded, "RNF128 deficiency aggravated allergic lung inflammation and promoted IL-5 and IL-13 production in lung ILC2s induced by A. alternata administration." Their results advocate for RNF128's role as more than just a peripheral player; it is, rather, pivotal to maintaining immune balance and controlling type 2 responses. This discovery opens avenues for future studies aimed at therapeutic interventions for individuals suffering from severe allergic conditions.