News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2016)

Research continues to support the involvement of innate lymphoid cells (ILCs) in mucosal immunity, and ILCs have been shown to display functional plasticity between group 1 ILCs (ILC1s) and group 3 ILCs (ILC3s). ILC1s, group 2 ILCs (ILC2s), and ILC3s are functionally similar to the subset of helper CD4+ T cells, TH1, TH2, and TH17 cells, respectively, which have also been shown to demonstrate similar plasticity. Silver et al (Nat Immunol 2016;17:626-35; https://doi.org/10.1038/ni.3443) show that ILC2s also exhibit plasticity when exposed to influenza virus or cigarette smoke through conversion of lung-resident ILC2s into ILC1s characterized by lower expression of the transcription factor GATA-3, which drives TH2 and ILC2 cells. Furthermore, these newly converted ILC1 cells produced IFN-γ, a cytokine typically produced by TH1 and ILC1 cells in response to inflammation. The authors determined that IL-12, which is required for TH1 differentiation, and IL-18, which is necessary for IFN-γ production, regulated this conversion, and during viral infection, ILC2 cells converged into inflamed areas and acquired an ILC1-like phenotype dependent on the TH1 and ILC1 transcription factor T-bet. Notably, the frequency of ILC1 cells in patients with chronic obstructive pulmonary disease correlated with disease severity and susceptibility to exacerbations, suggesting that ILCs might be a potential therapeutic target to treat acute -exacerbations. (Image used via Creative Commons license -BY-SA 2.0, with credit to user Jason Zack at en.wikipedia [CC BY-SA 2.5; http://creativecommons.org/licenses/by-sa/2.5].)ILC2s exhibit plasticity when exposed to influenza virus or cigarette smoke through conversion of lung-resident ILC2s into ILC1s ILC2s exhibit plasticity when exposed to influenza virus or cigarette smoke through conversion of lung-resident ILC2s into ILC1s Innate lymphoid cells (ILCs) have been shown to be sentinels of the immune system and provide a host of immunologic functions when challenged in mouse models. However, the function of ILCs in human subjects under natural conditions remains unclear. Vély et al (Nat Immunol 2016; https://doi.org/10.1038/ni.3553) studied ILCs in patients with severe combined immunodeficiency (SCID) who have mutations in the gene encoding the common γ-chain cytokine receptor subunit IL-2 receptor γ or the tyrosine kinase Janus kinase 3. The patients with SCID had defective T-cell development and deficiencies in natural killer cells, B cells, and myeloid cells and lacked all ILC subsets compared with healthy control subjects. When patients with SCID underwent hematopoietic stem cell transplantation in the absence of myeloablation, T cells were reconstituted, although numbers of ILCs were still considerably low. Remarkably, the persistent ILC deficiency over time (a follow-up period of 7-39 years) had no association with disease, and thus ILCs are likely dispensable in patients with a functional adaptive immune system, suggesting that they have overlapping characteristics with adaptive lymphocytes in human subjects under natural conditions.ILCs are likely dispensable in patients with a functional adaptive immune system ILCs are likely dispensable in patients with a functional adaptive immune system We asked the co-senior authors of this study for comment, Drs Alain Fischer and Eric Vivier. They write, “We think that our data are providing an alternative view of the immunological function of innate lymphoid cells (ILCs). In our study, human ILCs appear to be redundant in natural conditions, at least in the context of modern medicine and hygiene. Therefore, our findings support the notion as which the overlapping functions of ILCs and T cells contribute to the robustness of immunity and hence to the fitness of the host.” Asthma exacerbations are often associated with viral respiratory tract infections, with rhinovirus being the most common in adults. The antiviral cytokine interferon has been shown to be deficient during rhinovirus infection in asthmatic patients; however, the molecular underpinnings associated with this deficiency are not fully understood. Rupani et al (Am J Respir Crit Care Med 2016;194:26-37; https://doi.org/10.1164/rccm.201502-0280OC) sought to determine whether reduced Toll-like receptor 7 signaling is responsible for the impaired interferon responses to rhinovirus by asthmatic alveolar macrophages (AMs). The authors analyzed AMs from healthy subjects and patients with severe asthma (SA) and discovered that expression of Toll-like receptor 7 was significantly reduced in AMs of patients with SA and associated with reduced rhinovirus and imiquimod-induced interferon responses. Furthermore, AMs from patients with SA -expressed increased levels of 3 microRNAs (miR-150, miR-152, and MiR-375) that, when blocked, increased levels of TLR7 and virus-induced interferon production. These -results suggest that manipulation of the expression of these microRNAs can ameliorate the reduced expression of interferons, thus preventing rhinovirus-induced exacerbations in patients with SA.Interferon has been shown to be deficient during rhinovirus infection in asthmatic patients Interferon has been shown to be deficient during rhinovirus infection in asthmatic patients We asked author Dr Tilman Sanchez-Elsner of the University of Southampton, United Kingdom, to comment on the study. He writes, “This study shows, for the first time, that microRNAs can be used as targets to improve asthma virus-related exacerbations. It also places macrophages at the center of severe asthmatic patients’ deficiency ion producing anti-viral interferons.” Atopy is the tendency to produce IgE antibodies in response to exposure to allergens and is often a precursor for atopic dermatitis, food allergy, allergic rhinitis, and asthma. The condition has been linked recently to specific bacterial depletions in the infant gut at 3 months of age but not at 12 months. This led Fujimura et al (Nat Med 2016; https://doi.org/10.1038/nm.4176) to determine that compositionally and functionally distinct neonatal gut microbiota (NGM) states exist in ∼1 month olds, and are associated with significantly different relative risk of atopy at age 2 and asthma at age 4. Of the 3 NGM groups the authors describe, NGM 3 conferred a significantly higher risk of childhood atopy and asthma, and these subjects had a low abundance of bacterial taxa (Bifidobacterium, Akkermansia, and Faecalibacterium), a higher abundance of certain fungi (Candida and Rhodotorula) and a distinct fecal metabolome containing high levels of proinflammatory metabolites, compared to NGM1 and 2. Moreover, when sterile fecal water from NGM3 was cultured with adult human T cells, the proportion of IL-4–producing T cells (TH2 cells) was increased, while the proportion of CD25+FOXP3+ T cells (regulatory T cells) which are necessary to reduce proinflammation, was decreased. These findings demonstrate a link between the neonatal gut microbiome dysbiosis and CD4+ T-cell lineage that is associated with childhood atopy, which may lead to therapeutic interventions to replenish specific microorganisms to prevent disease development.A link between the neonatal gut microbiome dysbiosis and CD4+ T-cell lineage that is associated with childhood atopy A link between the neonatal gut microbiome dysbiosis and CD4+ T-cell lineage that is associated with childhood atopy News items were written by medical writer Kristina Bielewicz, MS.Find more News Beyond Our Pages online at www.jaci-nbop. blogspot.com. News items were written by medical writer Kristina Bielewicz, MS. Find more News Beyond Our Pages online at www.jaci-nbop. blogspot.com.