Innate lymphoid cells in asthma: Will they take your breath away?

Abstract

Asthma is a complex and heterogeneous disease that is characterized by airway hyperreactivity (AHR) and airway inflammation. Although asthma was long thought to be driven by allergen-reactive Th2 cells, it has recently become clear that the pathogenesis of asthma is more complicated and associated with multiple pathways and cell types. A very exciting recent development was the discovery of innate lymphoid cells (ILCs) as key players in the pathogenesis of asthma. ILCs do not express antigen receptors but react promptly to “danger signals” from inflamed tissue and produce an array of cytokines that direct the ensuing immune response. The roles of ILCs may differ in distinct asthma phenotypes. ILC2s may be critical for initiation of adaptive immune responses in inhaled allergen-driven AHR, but may also function independently of adaptive immunity, mediating influenza-induced AHR. ILC2s also contribute to resolution of lung inflammation through their production of amphiregulin. Obesity-induced asthma, is associated with expansion of IL-17A-producing ILC3s in the lungs. Furthermore, ILCs may also contribute to steroid-resistant asthma. Although the precise roles of ILCs in different types of asthma are still under investigation, it is clear that inhibition of ILC function represents a potential target that could provide novel treatments for asthma.

IgE‐expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy, and atopic dermatitis

“…We did not observe a correlation between IgE+ memory B‐cell and Th2 cell numbers, but we did find a positive correlation between Th2 cells and IgE+ plasmablasts. Previous studies show that type 2 innate lymphoid cells (ILC2) might play an important role in the local CSR toward IgE . Furthermore, expansions of ILC2 populations have been observed in allergic disease and are known to produce type 2 cytokines and ILC2 cells facilitate sensitization to local, but not systemic Th2 inducing allergen exposures .…”

Pathophysiology of severe asthma: We’ve only just started

“…Mechanisms to switch off type 2 immune responses in severe asthma may be impaired. Natural killer (NK) cells have innate immune functions similar to CD8 cells, in that they express perforin and granzyme and may play an important role in switching off activated immune cells by inducing apoptosis in granulocytes . They also induce apoptosis in eosinophils and are reduced in the blood of subjects with severe asthma compared with mild asthma and controls .…”

“…It involves the airway epithelium, fibroblasts, smooth muscle cells and innate immune cells, particularly dendritic cells and ILC . ILC are non‐T, non‐B lineage negative lymphocytes that migrate to the airways in response to environmental triggers (see Fig. ).…”

T cells in severe childhood asthma

“…The relative contributions of ILC2s and T cells to early events that govern certain facets of asthma continue to be debated, as evidenced by a recent report of a requirement for IL‐13 + CD4 + T cells, but not ILC2s, in the initiation of AHR . Beyond ILC2s, ILC3‐like cells that secrete IL‐17 have also been described in murine models (Table ), most notably in relation to obesity‐induced asthma and steroid‐resistant disease . ILCs may be particularly important in conditioning the lung immune response for the development of asthma, and this is elaborated on later.…”