Therapeutic targeting of innate immune pathways in respiratory disorders

Respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), lower respiratory infections, and acute respiratory distress syndrome (ARDS), continue to represent a significant health burden. In these diseases, the innate immune system is the body's first responder, orchestrating host defense against pathogens and inhaled irritants, but also contributing to tissue inflammation and damage when dysregulated. Recent advances have deepened our understanding of the roles that innate immune pathways (such as pattern recognition receptors, intracellular signaling pathways, cytokines, and innate immune cell regulation) play in both the initiation and resolution of respiratory pathology. With the evolution of genomics, advanced imaging, and molecular profiling, critical molecular nodes governing innate immunity in the respiratory tract are now being identified as promising druggable targets.

Despite major progress in our understanding, effective therapies that specifically modulate the innate immune response in respiratory diseases remain limited. Exaggerated or misdirected innate immunity is now recognized as a driver of both infectious and non-infectious respiratory disorders, fueling acute and chronic inflammation, airway remodeling, and acute exacerbations. The development of targeted therapeutics that can either dampen harmful inflammation or bolster insufficient immune responses offers significant hope for improving outcomes but also presents unique challenges in achieving selective modulation and avoiding unintended immunosuppression. This Research Topic aims to assemble cutting-edge research and reviews that address these challenges, highlight recent advances in therapeutic discovery, and explore innovative approaches for targeting innate immune pathways in respiratory disease settings.

We welcome original research articles, reviews, and perspectives addressing the therapeutic targeting of innate immune pathways in any aspect of respiratory disease. Topics of interest include but are not limited to:

• Molecular mechanisms underlying innate immune activation or suppression

• Identification and validation of druggable targets within innate immune cascades

• Preclinical and clinical studies of novel immunomodulatory agents

• Host-pathogen interactions and new antimicrobial strategies

• Modulation of innate immunity in allergic, inflammatory, or fibrotic lung diseases

• The use of biologics, small molecules, or nanoparticles for targeted delivery

• Biomarker development for patient stratification and treatment response

This Research Topic accepts submissions in the following formats: Brief Research Report, Case Report, Classification, Clinical Trial, Editorial, FAIR² Data, General Commentary, Hypothesis and Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Study Protocol, Systematic Review, and Technology and Code. All published articles will undergo rigorous external peer review and may be subject to publication fees.


Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Manuscripts focusing solely on cost-effectiveness studies are also not considered for publication in this journal.