Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 300 Longwood Ave, Boston, MA 02115, USA.
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 300 Longwood Ave, Boston, MA 02115, USA.
Trends Immunol. 2023 Oct;44(10):807-825. doi: 10.1016/j.it.2023.08.008. Epub 2023 Sep 14.
pH is tightly maintained at cellular, tissue, and systemic levels, and altered pH - particularly in the acidic range - is associated with infection, injury, solid tumors, and physiological and pathological inflammation. However, how pH is sensed and regulated and how it influences immune responses remain poorly understood at the tissue level. Applying conceptual frameworks of homeostatic and inflammatory circuitries, we categorize cellular and tissue components engaged in pH regulation, drawing parallels from established cases in physiology. By expressing various intracellular (pHi) and extracellular pH (pHe)-sensing receptors, the immune system may integrate information on tissue and cellular states into the regulation of homeostatic and inflammatory programs. We introduce the novel concept of resistance and adaptation responses to rationalize pH-dependent immunomodulation intertwined with homeostatic equilibrium and inflammatory control. We discuss emerging challenges and opportunities in understanding the immunological roles of pH sensing, which might reveal new strategies to combat inflammation and restore tissue homeostasis.
pH 值在细胞、组织和全身水平上都被严格维持，而 pH 值的改变——尤其是在酸性范围内——与感染、损伤、实体瘤以及生理和病理炎症有关。然而，在组织水平上，pH 值如何被感知和调节，以及它如何影响免疫反应，仍知之甚少。应用稳态和炎症回路的概念框架，我们对参与 pH 值调节的细胞和组织成分进行分类，从已建立的生理学案例中得出类比。通过表达各种细胞内（pHi）和细胞外 pH（pHe）感应受体，免疫系统可以将有关组织和细胞状态的信息整合到稳态和炎症程序的调节中。我们引入了抵抗和适应反应的新概念，以合理化与稳态平衡和炎症控制交织在一起的 pH 依赖性免疫调节。我们讨论了理解 pH 感应的免疫学作用所面临的新挑战和机遇，这可能揭示出对抗炎症和恢复组织稳态的新策略。
