Interleukin-22 and keratinocytes; pathogenic implications in skin inflammation

Masutaka Furue,Mihoko Furue

doi:10.37349/ei.2021.00005

Abstract

Interleukin (IL)-22 is produced from immune cells such as T helper (Th)22 cells, Th17/22 cells, and group 3 innate lymphoid cells. IL-22 signals via the IL-22 receptor 1(IL-22R1) and the IL-10 receptor 2 (IL-10R2). As the IL-22R1/IL-10R2 heterodimer is preferentially expressed on border tissue between the host and the environment, IL-22 is believed to be involved in border defense. Epidermal keratinocytes are the first-line skin barrier and express IL-22R1/IL-10R2. IL-22 increases keratinocyte proliferation but inhibits differentiation. Aryl hydrocarbon receptor (AHR) is a chemical sensor and an essential transcription factor for IL-22 production. In addition, AHR also upregulates the production of barrier-related proteins such as filaggrin in keratinocytes, suggesting a pivotal role for the AHR-IL-22 axis in regulating the physiological skin barrier. Although IL-22 signatures are elevated in atopic dermatitis and psoriasis, their pathogenic and/or protective implications are not fully understood.

Highlights

Interleukin (IL)-22 belongs to the IL-10-related cytokine family, which includes IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29 [1,2,3]
As the IL-22 receptor 1 (IL-22R1)/IL-10 receptor 2 (IL-10R2) heterodimer is preferentially expressed on border tissue between the host and the environment, IL-22 is believed to be involved in border defense
The IL-22 receptor (IL22R) is composed of a heterodimer of IL-22R1 and IL-10R2. The former protein is shared with the IL-20 and IL-24 receptor, while the latter is a component of the receptor for IL-10, IL-26, IL-28, and IL-29 [1,2,3]

Summary

Introduction

Interleukin (IL)-22 belongs to the IL-10-related cytokine family, which includes IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29 [1,2,3]. Recent therapeutic progress using biologics has demonstrated a critical pathogenic role for IL-4/IL-13-producing type 2 T helper (Th2) cells in atopic dermatitis and IL-17A-producing Th17 cells in psoriasis [4,5,6,7,8]. In addition to these essential axes, increased IL-22 signatures have been shown both in atopic dermatitis and psoriasis [9,10,11,12,13,14]. Non-lymphoid cells, including macrophages, neutrophils, mast cells, and fibroblasts may produce IL-22, but production in keratinocytes does not occur [1,2,3, 15, 17]. Th and Tc cells are subdivided into several specialized subsets depending on surface markers, cytokine production and the expression of critical transcription factors as exemplified in Table 1 [18]

Gene expression of critical transcription factors

Conclusion