Dysregulation of type 2 innate lymphoid cells and T H 2 cells impairs pollutant-induced allergic airway responses
Authors: Smitha Kumar
Leen J M Seys
Guy G Brusselle
Guy F Joos
Katrien C De Grove
Sharen Provoost
Rudi W Hendriks
Tania Maes
Andrew N J McKenzie
Journal: Journal of Allergy and Clinical Immunology (2017)
Discipline: IMMUNOLOGY
Keywords: Diesel exhaust particles; T(H)2 response; asthma; house dust mite; type 2 innate lymphoid cell.
Affiliations: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium. Electronic address: ., Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.

Abstract:  Background: Although the prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. Objective: We sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Methods: Wild-type, Gata-3+/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor Œ± (RORŒ±)fl/flIL7RCre (ILC2-deficient), and recombination-activating gene (Rag) 2-/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and TH2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Results: Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and TH2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and TH2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2-/- mice. Conclusion: These data indicate that dysregulation of ILC2s and TH2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure. 

Retracted: No

PubPeer comments:
 loose or missing assignment of image source  , 
 #1 Zoomed insets are created for the purpose of presenting a detailed image of a much larger field. Such insets often tell about the minute details that can be missed in a larger image. Often the authors try to zoom-in into a small portion of a much larger image where they want to show the microscopic changes that are taking place as a result of some reaction or a therapeutic response. These zoomed insets are carefully selected so as to show the best microscopic view and it is often seen that they may not overlap with the larger-picture. In my honest opinion there is nothing wrong if the zoomed inset does not match with the main image as long as there is no manipulation, image duplication, or any other act of deceiving is involved. The concern by Geranium in #1 appears to be in-valid because there is no act of deception involved. Moreover, it is up to the authors to select the best zoomed-in image which helps the readers to appreciate their work. It is not always essential that the zoomed-in inset has to be a part of the same larger image described next to it. I am presenting one example below from a published paper which can help the readers understand this issue in a better way. DOI : 10.1007 s40097-014-0136-8  Above figure (Fig 2) from the paper entitled  Goldu2013platinum alloy nanoparticles through water-in-oil microemulsion also shows a main image with a zoomed-inset. Even though it appears that the image and inset are different; but it can be seen that the inset is  the best representative of a large picture as it clearly tells about the minute details and other intricacies. In my opinion the comment in #1 is superficial and does not dilute the scientific soundness of the work. ,