Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity

By Ya‐Jen Chang, H. Y. Kim, L. Albacker, N. Baumgarth, Andrew N. J. McKenzie, Dirk E. Smith, R. DeKruyff, D. Umetsu. Nature Immunology, 2011

774 citations recorded by the source corpus.

Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (TH2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)–IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.

Subfields: Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/e1945f299df4882af674b91b16f216e99a1cc98f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. R. Locksley
2. C. Cayrol
3. H. Spits
4. J. Girard
5. S. V. Van Dyken
6. A. Chawla
7. Andrew N. J. McKenzie
8. D. Umetsu

In Physiology

1. R. Locksley
2. A. Chawla
3. Ari B. Molofsky
4. J. Nussbaum
5. Hong-Erh Liang

Citations in the corpus

• Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. (2012, background): “Recently, Chang et al. (2011) reported the presence of Lin ST2+Sca-1+c-kit+ cells in virus-infected BALB/c mouse lung and indicated their importance in viral-induced airway inflammation and macrophage infiltration.”
• Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation (2014, background): “, 2010) and airway mucosa of mice (Chang et al., 2011; Halim et al., 2012a; Monticelli et al., 2011) and man (Mjösberg et al.”
• The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. (2012, positive): “Furthermore, ILC2s are involved in influenza virus-mediated airway hyperreactivity by promoting inflammation (Chang et al., 2011).”
• Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages (2013, background): “…the major innate cell source of these cyto kines, and loss of these cells can compromise the host type 2 immune response (Brickshawana et al., 2011; Chang et al., 2011; Mjösberg et al., 2011; Moro et al., 2010; Neill et al., 2010; Price et al., 2010; Halim et al., 2012; Ikutani et al., 2012;…”
• IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. (2014, background): “Activation of lung ILC2s by IL-33 was also shown to mediate influenza-induced airway hyper-reactivity independently of adaptive immunity [19].”
• MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion (2014, background): “In addition to antihelminthic immunity, ILC2s have also been implicated in promoting detrimental type-2 immune responses in mouse models of asthma (Barlow et al., 2012; Chang et al., 2011; Monticelli et al., 2011) and allergies (Bartemes et al.”
• Innate lymphoid cells and asthma. (2014, positive): “2 (CD90), and ST2, and did not occur in ST2 mice.(14) Influenza-induced AHR was dependent on IL-13, and adoptive transfer experiments demonstrated that IL-13–secreting ILC2s were capable of restoring AHR in IL-13 hosts.”