pH sensing and inflammation: linking acidic microenvironments to immune reprogramming

Area of Science:

• Immunology
• Cellular Physiology
• Molecular Biology

Background:

• Traditionally, pH was viewed as a metabolic byproduct.
• Emerging evidence highlights pH as an active signaling cue modulating inflammation via proton-sensing receptors.
• Tissue acidification is common in pathological conditions like infection, ischemia, and cancer.

Purpose of the Study:

• To systematically review recent advances in pH sensing in inflammation regulation.
• To explore the structural classes, distribution, and function of pH sensors.
• To examine the integration of acidic signals in inflammatory networks and their therapeutic potential.

Main Methods:

• Literature review focusing on pH sensing mechanisms in inflammation.
• Analysis of proton-sensing receptors including GPCRs, ASICs, and TRP channels.
• Investigation of pH-responsive regulatory factors like BRD4 and HIF-1α.

Main Results:

• Diverse pH sensors (GPCRs, ASICs, TRP channels) detect acidic microenvironments.
• Acidic conditions influence immune cell function, mediator release, and tissue injury.
• pH sensors initiate signaling cascades and gene expression changes impacting inflammation.

Conclusions:

• The "pH-sensor-inflammation" axis is a significant paradigm in immune regulation.
• pH sensing plays critical roles in both immune homeostasis and pathological inflammation.
• Emerging opportunities exist for pH-based diagnostics and targeted therapies.