Presenting Author: Seung Hyeon Kim
, Postdoc at Univ. of Illinois Col. of Med.
Abstract:
Our understanding of lung microbial ecology underscores the impact of diseases on microbe-host interactions, influencing lung disease pathogenesis. However, the intricate mechanisms governing host immune responses and the lung microbiome remain incompletely elucidated. IL-10, an anti-inflammatory cytokine, crucially modulates immune responses, yet the significance of the IL-10/IL-10 receptor (IL-10R) axis in maintaining lung homeostasis is unknown. We found that IL-10R signaling in lung interstitial macrophages (IMs) preserves balanced lung microbiota, contributing to homeostasis. The lack of IL-10 surprisingly triggered spontaneous lung inflammation, progressing to pulmonary fibrosis without external factors. IL-10R deficiency in CX3CR1-expressing MHC IIhi IMs led to inflammatory phenotypes similar to IL-10-deficient mice. 16S bacterial rRNA sequencing identified dominant colonization of Proteobacteria (e.g., D. acidovorans) and Actinobacteria (e.g., R. erythropolis) in IL-10R-deficient CX3CR1-expressing MHC IIhi IMs mice lungs. Lung inflammation occurred in germ-free (GF) IL10-/- mice after commensal colonization, while GF IL10+/+ mice remained unaffected. Using human fecal microbiota transplantation, we observed that human gut commensals induce lung inflammation in GF IL-10-/- mice. These results highlight the roles of IL-10R-expressing MHC IIhi IMs in lung homeostasis, regulating the interaction between host immune responses and commensal microbiota.
IL10 signal of lung interstitial macrophages prevents progressive lung fibrosis by suppressing commensal dysbiosis
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 05:45 PM to 06:00 PM Room: Room W181