The emerging role of type 2 inflammation in asthma

ABSTRACT

Introduction: Bronchial asthma (BA) is a chronic airways inflammatory disease. Based on the biological mechanisms that underline the disease, asthma has been classified as type 2 or non-type 2 phenotype.

Areas covered: An emerging role has been identified for group 2 innate lymphoid cells (ILC2s) able to produce the classical type 2 cytokines. The role of Th2 cells and IL-4 is crucial in the pathogenesis of allergic BA as supported by asthma models. IL-13, shares many biological functions with IL-4 such as induction of IgE synthesis and regulation of eosinophil trafficking. However, IL-13 does not induce Th2 cell differentiation. The Authors reviewed evidence on the new concept of type 2 inflammation and the cellular and molecular network behind this process. Literature data in the PubMed were analyzed for peer-reviewed articles published until September 2020.

Expert opinion: The current trend is to consider Th2- and ILC2-driven pathways as two separate pathogenic mechanisms, recent data underscore that adaptive Th2- and innate cell responses represent two integrated systems in the production of IL-4, IL-5, and IL-13 leading to the current ‘concept’ of type 2 inflammation. This review highlights the role of Th2 cells and ILC2 in the recent new concept of type 2 inflammation.

KEYWORDS:

• Asthma
• ilc2
• th2 cells
• th2 cytokines
• type 2 inflammation

Article highlights

• Asthma is complex a disease, and may be caused by a variety of different mechanisms.

• Asthma is not a single disease but instead a variable condition in terms of clinical presentations (phenotypes) and distinct underpin pathophysiological mechanisms (endotypes).

• The only way to develop a personalized therapeutic approach is to define phenotype/endotype in a single subject.

• Not only adaptive immune cells but also innate cells play a role in the pathogenesis of airway inflammation in asthma.

• The key cytokines traditionally referred to as Th2 cytokines such as IL-4, IL-5, and IL-13 are produced by both Th2 cells (adaptive response) and ILC2 (innate response).

• Adaptive Th2- and innate cell responses represent two integrated systems leading to the current ‘concept’ of type 2 inflammation.

Declaration of interest

The authors AM, AV, have received speaker’s honoraria from Sanofi, AstraZeneca, GSK, Novartis, and Chiesi EM have received speaker’s honoraria from Sanofi, AstraZeneca, GSK, Novartis. SB reports personal fees from GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.