Type 2 innate lymphoid cells: new players in asthma and allergy

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Two years ago, T helper cells, including Th1, Th2 and Th17 cells, were considered to be the most significant sources of cytokine during the orchestration of immune responses in the lung. Following the discovery of innate lymphoid cells, we now know that these previously unappreciated cytokine-secreting cells, including ILC1 (IFN-γ-expressing NK cells), ILC2 (IL-5 and IL-13-expressing nuocytes) and RORγ ILC (IL-17 and IL-22-expressing ‘ILC3’) are important mediators in immune processes. Herein we review the role of ILC2 specifically in inflammatory lung responses with special attention to allergen-induced and viral-induced type 2 lung disease.

Highlights

► ILC2 play a critical role in type 2 immunity. ► ILC2 proliferate during experimental asthma responses. ► IL-13 production by ILC2 contributes to allergic asthma.

Introduction

An essential component of effective host cell-mediated immunity is the co-ordinated crosstalk between its innate and antigen-specific adaptive arms. Nowhere is this more crucial than at mucosal surfaces, such as the lung, which serve as the barrier between the external and the sterile internal environments, where both pathogenic microorganisms and innocuous substances such as commensal bacteria and inhaled antigens are frequently encountered. Several different populations of innate-like lymphocytes, including natural killer (NK) cells [1], γδ T cells [2] and CD1d-restricted NKT cells [3] have been previously implicated in the regulation of immune responses in the respiratory tract. This review will focus on the roles of the recently discovered population of type 2 innate lymphoid cells (ILC2), which reside at the nexus between innate and adaptive immunity in directing type 2 inflammatory responses and may additionally participate in lung remodelling and repair (Figure 1).

Section snippets

Definition

Innate lymphoid cells (ILCs) have a morphology typical of lymphocytes, but lack rearranged antigen receptors, and are currently grouped into three known subsets: NK cells, RORγt-dependent ILCs and RORα-dependent ILCs (referred to herein as ILC2) [4••, 5]. The latter two populations lack cell surface markers associated with other major hematopoetic lineages and express CD25 (IL-2Rα), CD90 (Thy1), CD117 (c-Kit) and CD127 (IL-7Rα). Additionally, ILC2 express CD278 (ICOS), ST2 (IL-33R) and IL-17BR,

Future directions

ILC2, a cell population that serves as a crucial link between innate immunity and the type 2 adaptive immune response, appears to play important roles in the lung including responses to parasitic helminths, tissue repair and the pathogenesis of allergic asthma. In order to effectively design therapeutic agents, further studies are needed in several areas to better understand ILC2 function.

Trafficking: What are the signals that are responsible for the transit of ILC2 into the lung? It has been

Conclusion

After so long in obscurity, the discovery of ILCs has changed our perception of T cells as the major cytokine-secreting regulators of immunity and made us aware of completely unappreciated innate immune cell sources of regulatory cytokines. The goal is now to define their place in immunity and disease.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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