Jerry (Jaewon) Cho
Postdoctoral Trainee
Department of Pharmacology & Regenerative Medicine
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Mentor: Ki-Wook Kim
Co-Mentor: Teruyuki Sano
Title: Mechanistic Insights into Commensal Microbiota–Driven Pulmonary Inflammation Along the Gut–Lung Axis
Chronic pulmonary inflammation is increasingly recognized as an extra-intestinal manifestation of inflammatory bowel disease (IBD), but the gut–lung mechanisms remain unclear. In IL-10R–deficient mice, interstitial macrophages (IMs) expand and drive age-dependent peribronchiolar inflammation and follicular bronchiolitis, whereas alveolar macrophages remain unaffected. Lung pathology is prevented by antibiotics and induced by human fecal microbiota transplantation (huFMT), demonstrating that commensal microbiota are essential drivers of this process.
Two potential mechanisms may explain how gut microbes promote lung inflammation: (i) direct microbial translocation from the gut to the lung, or (ii) migration of gut-resident immune cells into the pulmonary niche. Aim 1 addresses these pathways through dual RNA-seq, CFU assays, bacteria-specific qPCR, and photo-convertible Il10-deficient KikGreen/Red mice. Aim 2 investigates how microbial metabolites and pathogen-associated molecular patterns (PAMPs) activate stromal and immune compartments via TLR signaling, using epithelial-, endothelial-, and myeloid-specific knockouts of CSF1 and TLR2/4 in an IL-10R–deficient background.
These studies aim to elucidate how commensal microbiota orchestrate pulmonary macrophage activation and chronic inflammation, thereby providing mechanistic insight into the gut–lung axis and its cellular and molecular interactions