TRPV1: The key bridge in neuroimmune interactions

Abstract

The nervous and immune systems are crucial in fighting infections and inflammation and in maintaining immune homeostasis. The immune and nervous systems are independent, yet tightly integrated and coordinated organizations. Numerous molecules and receptors play key roles in enabling communication between the two systems. Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a non-selective cation channel, recently shown to be widely expressed in the neuroimmune axis and implicated in neuropathic pain, autoimmune disorders, and immune cell function. TRPV1 is a key bridge in neuroimmune interactions, allowing for smooth and convenient communication between the two systems. Here, we discuss the coordinated cross-talking between the immune and nervous systems and the functional role and the functioning manner of the TRPV1 involved. We suggest that TRPV1 provides new insights into the collaborative relationship between the nervous and immune systems, highlighting exciting opportunities for advanced therapeutic approaches to treating neurogenic inflammation and immune-mediated diseases.

Keywords: Immune system; Nervous system; Neuroimmune interaction; TRPV1.

Figure 1

The effect of TRPV1 on the immune system. Many external factors, such as capsaicin, noxious heat, acidic solutions, and physical damage, as well as immune challenges, rapidly activate TRPV1, resulting in the release of neuropeptides such as CGRP and SP. These neuropeptides activate immune cells, including macrophages, T cells, and neutrophils, and exert various effects that influence immune cell proliferation, differentiation, death, recruitment, and activation. These changes in cell activity may lead to proinflammatory or anti-inflammatory effects under different disease contexts (The picture was made using Figdraw).

Figure 2

The effect of inflammatory mediators on TRPV1 and neurological disease. TRPV1 can be sensitized by many inflammatory mediators and exacerbate neurological disorders. For example, elevated levels of histamine, Leukotriene B4, and IL-31 lead to TRPV1 activation and induce itch., , Increased TNF-α and IGF-1 induced the upregulation of TRPV1 expression and enhancement of pain., Increased levels of proinflammatory factors, including IL-1β, IL-6, TNF-α, and HMGB1, resulted in TRPV1 activation and frequently repetitive febrile seizures. (The picture was made using Figdraw). CNS: Central nervous system; HMGB1: High mobility group box-1 protein; IGF-1: Insulin-like growth factor-1; IL: Interleukin; TNF-α: Tumor necrosis factor-α; TRPV1: Transient receptor potential vanilloid subfamily member 1.