# Cross-Talk between Neurons and Immune Cells in Pruritus: from Mechanisms To Medicines

## TL;DR

This paper reviews how neurons and immune cells interact to cause chronic itching and how these interactions can be targeted for treatment.

## Contribution

The paper highlights new insights into the role of mediators like periostin and BNP in linking immune and neural pathways in chronic pruritus.

## Key findings

- Type 2 cytokines like IL-4 and IL-13 activate pruriceptive neurons through TRPV1/TRPA1 channels.
- Periostin connects immune and neural pathways by inducing macrophage IL-31 release.
- BNP facilitates itch signaling in the spinal cord and promotes keratinocyte production of itch mediators.

## Abstract

Chronic pruritus (CP) is among the most distressing symptoms and has a complex pathophysiology. This review aims to describe the mediators and mechanisms of neuroimmune crosstalk—a term referring the bidirectional interactions between the nervous and immune systems that underly itch pathogenesis and chronicity.

Type 2 cytokines (IL-4, IL-13, IL-31) directly activate pruriceptive neurons, resulting in itch sensation and nerve fiber sensitization via TRPV1/TRPA1, whereas keratinocyte-derived alarmins (TSLP and IL-33) amplify neural activation. Periostin, an emerging downstream mediator, binds integrin αVβ3 on neurons and induces macrophage IL-31 release, representing a link between immune and neural pathways. BNP, another emerging mediator that is co-expressed with IL-31, facilitates itch signaling in the spinal cord and induces keratinocyte production of itch mediators, highlighting its integral role in neuroimmune signaling.

CP arises from a complex interplay between the immune system, sensory neurons, and keratinocytes. The success of therapeutic advances targeting cytokines, neuropeptides, and their receptors in recent years have confirmed the importance of understanding these complex underlying networks.