Enhanced innate type 2 immune response in peripheral blood from patients with asthma

Abstract

Background In mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood. Objective The goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in human asthma. Methods Peripheral blood mononuclear cells (PBMCs) from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy controls (HC) were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs. Results Human PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage−CD127+CRTH2+ cells, responded to IL-33 and produced large quantities of IL-5 and IL-13, but undetectable IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 compared to subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group compared to the AR or HC groups. Conclusion Innate type 2 immune responses are increased in asthma but not in allergic rhinitis, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.

T cells are necessary for ILC2 activation in house dust mite‐induced allergic airway inflammation in mice

“…Particularly, since recent studies in human provided evidence that ILC2s may be responsible for steroid-resistant asthma. ILC2 numbers are increased in sputum and peripheral blood of patients with severe asthma compared to mild asthmatics or healthy controls [45,46]. Importantly, evidence was found for a role of uncontrolled localized production of IL-5 and IL-13 by a steroid-insensitive population of ILC2s, in agreement with in vitro studies showing that ILC2s are steroidinsensitive in the presence of TSLP [46,47].…”

Innate Lymphoid Cells in Type 2 Immune Responses

“…Whilst the physiological role of ILC2 in human airway inflammation is not fully understood, ILC2 were shown to be elevated in nasal biopsies of chronic rhinosinusitis patients as compared to healthy controls (Mjosberg et al 2011) demonstrating an association of these cells with human disease. Moreover, a recent report has shown that the prevalence of ILC2 in the blood of allergic asthma patients was substantially higher than either allergic rhinitis patients or healthy controls (Bartemes et al 2014). These results are consistent with a role for ILC2 in the immunopathology of allergic asthma in humans.…”

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

“…45 Increased ILC2s are found in blood of asthma patients, and these cells produced more IL-5 and IL-13 in response to IL-25 or IL-33 compared to healthy controls or AR patients. 46 Whereas similar peripheral blood ILC2 proportions were found in asthma patients and controls in an earlier study, 47 the finding of increased ILC2 numbers in patients with asthma was confirmed by several subsequent reports. 42,48,49 Taken together, these studies suggest the involvement of ILC2s in specific subgroups of asthma ( Figure 1).…”