Innate lymphocyte cells in asthma phenotypes

Abstract

T helper type 2 (TH2) cells were previously thought to be the main initiating effector cell type in asthma; however, exaggerated TH2 cell activities alone were insufficient to explain all aspects of asthma. Asthma is a heterogeneous syndrome comprising different phenotypes that are characterized by their different clinical features, treatment responses, and inflammation patterns. The most-studied subgroups of asthma include TH2-associated early-onset allergic asthma, late-onset persistent eosinophilic asthma, virus-induced asthma, obesity-related asthma, and neutrophilic asthma. The recent discovery of human innate lymphoid cells capable of rapidly producing large amounts of cytokines upon activation and the mouse data pointing to an essential role for these cells in asthma models have emphasized the important role of the innate immune system in asthma and have provided a new means of better understanding asthma mechanisms and differentiating its phenotypes.

Keywords: Airways; Asthma; Cytokines; Innate immunity; Phenotype.

Fig. 1

Function and regulation of group 2 lymphoid cells in different asthma phenotypes. Innate lymphoid cells group 2 (ILC2s) of early onset asthma and late onset asthma with polyposis are regulated by several elements such as the epithelial cell derived thymic stromal lymphopoietin (TSLP), interleukin 25 (IL-25) and IL-33; arachidonic acid metabolites, like prostaglandin D₂ (PGD2) and leukotriene D₄ (LTD₄). Lung ILC2s produces IL-9 that also regulates their activation. ILC2s release IL-4, IL-5 and IL-13; then increase the airway hyperreactivity and eosinophilia. Lung ILC2s also secrete arginase 1. ILC2s can stimulate naive T cells (TH0) by IL-4, costimulatory molecules OX40L and a contact-dependent mechanism favoring T_H2 polarization. In the virus induced asthma phenotype, lungs ILC2s constitute a balance between tissue repair and tissue damage via amphiregulin and type 2-cytokine secretion. The damage is potentialized by IL-33 and the repairing capacity is enhanced by maresins. Eos, eosinophil

Fig. 2

Mechanism of innate lymphoid cells group 3 in obesity induced asthma and their regulation. Innate lymphoid cells group 3 (ILC3s) produce interleukin 17A (IL-17A) and IL-22. Macrophages (Mϕ) produce IL-1β that engages IL-1 receptor on innate lymphoid cells group 3 (ILC3s) resulting in airway hyperreactivity. This effect can be inhibited by an IL-1 receptor (IL-1R) antagonist. ILC3s are sensitive to environmental factors, micronutrients and microbiota. Vitamin D deficiency increases ILC3s’ functions whereas Vitamin A deficiency leads to a reduction; the influence of airway microbiota on ILC3s is still unknown