IMMUNOLOGY2026™ Conference Recordings For Attendees-pH-Dependent Innate Immune Circuitry Confers Tolerance to Systemic Inflammation

pH-Dependent Innate Immune Circuitry Confers Tolerance to Systemic Inflammation

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Video Summary

Xu from Harvard Medical School and Boston Children’s Hospital described unpublished work showing how pH sensing by the immune receptor GPR65 helps control inflammation. His team found that GPR65 is highly expressed in certain immune cells and becomes active within normal tissue pH ranges. In mouse models, GPR65 deficiency did not affect bacterial clearance but greatly increased lethality during LPS-induced sepsis, due to severe acidosis and excessive inflammation. The key mechanism involved macrophages: GPR65 signaling caused early production of IL-10, which suppressed IL-1β and IL-23, limiting γδ T cell production of IL-17, a cytokine that drove death. Without GPR65, IL-10 came too late to restrain this pathway. Single-cell and in vitro studies showed that pH-dependent GPR65 signaling shifts macrophages toward anti-inflammatory, tissue-repair programs. Overall, the work suggests tissue pH acts as an immune checkpoint that balances host defense and inflammatory damage.

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Date April 18, 2026 1:45 PM - 2:00 PM

Room 156

Session Microenvironmental Influences on Innate Immunity

Speaker Xu Zhou

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

Year 2026

Keywords

GPR65

pH sensing

sepsis

IL-10

macrophage inflammation

April 18, 2026 1:45 PM - 2:00 PM

156

Microenvironmental Influences on Innate Immunity

Xu Zhou

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

2026