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Review
. 2021 Dec;51(12):1538-1552.
doi: 10.1111/cea.14029. Epub 2021 Oct 15.

Type 2 immunity-driven diseases: Towards a multidisciplinary approach

Dorian Hassoun  1 , Olivier Malard  2 , Sébastien Barbarot  3 , Antoine Magnan  4 , Luc Colas  5   6
Affiliations
Review

Type 2 immunity-driven diseases: Towards a multidisciplinary approach

Dorian Hassoun et al. Clin Exp Allergy. 2021 Dec.

Abstract

Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL-4, IL-5, IL-13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2-targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field.

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Conflict of interest statement

DH declares the following conflict of interest: Support for attending meetings and/or travel from SANOFI, Novartis, GSK and AstraZeneca. OM declares the following link of interest: Adviser, and/or clinical study investigator for Medtronic, Sanofi‐Genzyme, GSK, Novartis, MSD, ALK. SB declares the following conflict of interest: Scientific adviser, consultant, and/or clinical study investigator for Almirall, Sanofi‐Genzyme, Abbvie, Novartis, Janssen, Leo‐Pharma, Pfizer, Eli Lilly, UCB Pharma. AM declares the following conflict of interest: Consultant or investigator for Novartis, GSK, SANOFI & Astra Zeneca. LC declares the following link of interest: Support for a PhD.

Figures

FIGURE 1
FIGURE 1
Phenotypic traits and main endotypes of environment‐driven diseases. Type 2 immunity is implicated only in a small proportion of patients affected by chronic rhinitis, asthma and atopic dermatitis. Created with BioRender.com
FIGURE 2
FIGURE 2
Type 2 inflammation in environment‐driven diseases. Diverse environmental aggression activates innate and adaptative immunity towards type 2 polarization. The epithelium plays an important role not only as an activator but also as a collateral target of inflammation. Eosinophilic infiltration and basophil and mast cell degranulation upon renewed stimulation induce oedema and critical tissue remodelling. Overall, tissue inflammation and epithelial dysfunction lead to hallmarks of cutaneous and respiratory symptoms. Abbreviations: AD, atopic dermatitis; AHR, airway hyperresponsiveness; CRSwNP, chronic rhinosinusitis with nasal polyposis; IgE, Immunoglobulin E, IL, interleukin; ILC2, group 2 innate lymphoid cell; TSLP, hymic stromal lymphopoietin. Created with BioRender.com
See this image and copyright information in PMC

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