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Review
. 2022 Jul 13:13:930862.
doi: 10.3389/fimmu.2022.930862. eCollection 2022.

The Therapeutic Potential for Targeting Group 2 Innate Lymphoid Cells in Asthma

Takahiro Matsuyama  1 , Hiromi Matsuyama  1 , Yoichi Dotake  1 , Koichi Takagi  1 , Kentaro Machida  1 , Hiromasa Inoue  1
Affiliations
Review

The Therapeutic Potential for Targeting Group 2 Innate Lymphoid Cells in Asthma

Takahiro Matsuyama et al. Front Immunol. .

Abstract

T helper type 2 cells (Th2 cells) and group 2 innate lymphoid cells (ILC2s) play an important role in the pathophysiology of asthma, including airway eosinophilic inflammation. ILC2s are activated by epithelial-derived cytokines [interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP)] from airway epithelial cells, leading to the release of high amounts of type 2 cytokines, such as IL-5 and IL-13. ILC2s induce airway inflammation in an antigen-independent manner, and ILC2s are considered to be involved in the pathogenesis of asthma exacerbation. Furthermore, ILC2 activation might also confer steroid resistance. Many recent studies in humans and mice are increasingly demonstrating that the function of ILC2s is regulated not just by epithelial-derived cytokines but by a variety of cytokines and mediators derived from innate immune cells. Furthermore, the biologics targeting these cytokines and/or their receptors have been shown to reduce asthma exacerbations and improve lung function and quality of life in asthmatics. This article reviews the current treatment landscape for type 2 airway inflammation in asthma and discusses the therapeutic potential for targeting ILC2s.

Keywords: airway inflammation; asthma; biologics; group 2 innate lymphoid cells (ILC2s); innate immune network.

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Conflict of interest statement

HI reports grants from Boehringer Ingelheim, Novartis and GlaxoSmithKline unrelated to this study; and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Kyorin, and Sanofi. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The network between ILC2s and cells of the innate and adaptive immune system and a schematic of investigative and approved biologic therapies. Biologics target IgE, IL-5 and its receptor, IL-4 receptor, and alarmins such as TSLP and IL-33, leading to the suppression of asthma exacerbation and improved asthma control. Tiotropium suppresses basophil-derived IL-4 production, and R848, a toll-like receptor7 (TLR7) agonist, induces macrophage-derived IL-27 production. These pathways also indirectly induce the suppression of ILC2-mediated airway eosinophilic inflammation. ILC2, type 2 innate lymphoid cell; M3R, muscarinic M3 receptor.
See this image and copyright information in PMC

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