IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs

Abstract

Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.

Efficacy of Curcumin as an Immunostimulatory Dietary Supplement for Channel Catfish

“…Furthermore, our results revealing lower concentration of IL-12 due to curcumin supplementation are in accordance with similar studies (Kang et al, 1999). Together, IL-4, IL-12, IL-1β play an important role in innate lymphocytes in human inflammation (Bal et al, 2016). IL-12 can also stimulate similar functions to IL-2, an essential T-cell proliferation and differentiation factor in the specific immune system (Bachmann and Oxenius, 2007).…”

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

“…35 Human data are scarce, but in mice, IL-17A producing ILC3s were implicated in obesity-induced asthma, 51,52 indicating a possible role for IL-1b 51 as this cytokine can stimulate both ILC2s and ILC3s. 6,53,54 In a pilot study, IL-17A-producing lineage negative cells in BAL were demonstrated to be enriched in patients with severe asthma. 51 So far, no other studies have been performed analyzing ILC subsets in patients with Th2-low asthma.…”

“…In nonresolving chronic inflammatory Th1-like diseases including Crohn's disease 5 and chronic pulmonary obstructive disease (COPD), the number of ILC1s remains elevated. 6 …”

“…14 In a different study, GOLD stage IV patients had significantly more ILC3s and ILC1s, due to the differentiation of ILC2s into ILC1s. 6 Elevated ILC1 numbers were also found in peripheral blood of COPD patients, correlating with disease severity and susceptibility to exacerbations. 56 Recently, ILC3s were detected in inflammatory aggregates and near blood vessels in lungs of smokers and COPD patients providing insight into the initiation of smoke-induced ectopic pulmonary lymphoid aggregates ( Figure 1).…”

“…To translate in vitro findings of potential drug candidates in in vivo models, humanized mice (mice with a humanized immune system) are an excellent tool to study ILCs. 6,98 In this manner, several ILC2-targeting options have already been evaluated.…”