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Front. Immunol. | doi: 10.3389/fimmu.2018.02752

Repetitive exposure of IL-17 into the murine air pouch favours the recruitment of inflammatory monocytes and the release of IL-16 and TREM-1 in the inflammatory fluids

  • 1Università degli Studi di Napoli Federico II, Italy
  • 2University of Birmingham, United Kingdom
  • 3Medizinische Fakultät, Universitätsklinikum Magdeburg, Germany
  • 4Department of Life Sciences, University of Roehampton, United Kingdom
  • 5William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom

The infiltration of Th17 cells in tissues and organs during the development of many autoimmune diseases is considered a key step towards the establishment of chronic inflammation. Indeed, the localized and prolonged release of IL-17 in specific tissues has been associated with an increased severity of the inflammatory response that remains sustained over time. The cellular and molecular mechanisms behind these effects are far from being clear.
In this study we investigated the effects of two repetitive administration of recombinant IL-17 into the murine air pouch to simulate a scenario where IL-17 is released over time in a pre-inflamed tissue. Consistent with our previous observations, mice receiving a single dose (primary) of IL-17 showed a transitory influx of neutrophils into the air pouch that peaked at 24 hours and declined at 48 hours. Conversely, mice receiving a double dose of the cytokine – one at time 0 and the second after 24hr – showed a more dramatic inflammatory response with almost 2-fold increase in the number of infiltrated leukocytes and significant higher levels of TNF- and IL-6 in the inflammatory fluids. Further analysis of the exacerbated inflammatory response of double-injected IL-17 mice showed a unique cellular and biochemical profile with inflammatory monocytes as the second main population emigrating to the pouch and IL-16 and TREM-1 as the most upregulated cytokines found in the inflammatory fluids. Most interestingly, mice receiving a double injection of IL-1β did not show any change in the cellular or biochemical inflammatory response compared to those receiving a primary injection or just vehicle.
Collectively these results shed some light on the function of IL-17 as pro-inflammatory cytokine and provide possible novel ways to target therapeutically the pathogenic effects of IL-17 in autoimmune conditions.

Keywords: Chemokines, Cytokines, IL-17, TREM, Inflammation

Received: 16 Aug 2018; Accepted: 08 Nov 2018.

Edited by:

Diana Boraschi, Istituto di biochimica delle proteine (IBP), Italy

Reviewed by:

Vincenzo BRANCALEONE, University of Basilicata, Italy
Jonathan Noonan, University of Glasgow, United Kingdom  

Copyright: © 2018 Maione, Iqbal, Beyrau and D'Acquisto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Fulvio D'Acquisto, Department of Life Sciences, University of Roehampton, London, EC1M 6BQ, United Kingdom, f.dacquisto@qmul.ac.uk