IMMUNOLOGY2026™ Conference Recordings For Attendees-How do tissues sense proteolytic stress?

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Video Summary

The talk described how tissues sense and adapt to proteolytic stress, focusing on lung responses to proteases such as LASB, papain, and subtilisin. Acute exposure caused vascular damage, red blood cell leakage, heme release, and impaired lung function. However, repeated exposure over three days led to tissue adaptation, reduced damage, and improved respiratory outcomes. Bulk and single-cell RNA sequencing identified NRF2 signaling in alveolar macrophages as a key protective program. These macrophages sensed heme from damaged vessels and activated heme-oxidation pathways, converting toxic heme into bilirubin. Bilirubin then stimulated fibroblasts to produce serine protease inhibitors, which helped suppress proteolytic activity and protect tissue. Depleting alveolar macrophages abolished this adaptation. Overall, the study showed that prolonged proteolytic stress triggers a macrophage-fibroblast circuit that promotes tissue protection and limits damage.

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Date April 18, 2026 2:00 PM - 2:15 PM

Room 156

Session Microenvironmental Influences on Innate Immunity

Speaker Karen Agaronyan

Track Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Year 2026

Keywords

proteolytic stress

alveolar macrophages

NRF2 signaling

heme oxidation

fibroblast protection

April 18, 2026 2:00 PM - 2:15 PM

156

Microenvironmental Influences on Innate Immunity

Karen Agaronyan

Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

2026