<em>Mucosal associated invariant T cells are deficient in human airways diseases</em> — ASN Events
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Mucosal associated invariant T cells are deficient in human airways diseases (#103)

Timothy SC Hinks 1 2 , Joshua C Wallington 2 , Karl J Staples 2 3 , Anthony P Williams 3 , Tom MA Wilkinson 1 2 , Ratko Djukanovic 1 2 , Stephan D Gadola 4
  1. Southampton NIHR Respiratory Biomedical Research Unit, Southampton, Hampshire, United Kingdom
  2. Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom
  3. Wessex Investigational Sciences Hub Laboratory, University Hospital Southampton, Southampton, Hampshire, United Kingdom
  4. Novartis Institute of Biomedical Research, Novartis, Basel, Switzerland

Introduction

The role of invariant NKT cells in airways disease has provoked much interest and controversy, but mucosal associated invariant (MAIT) cells have not been studied in the human airways. Infection with non-typable haemophilus influenzae (NTHi) is linked to recurrent exacerbations and disease progression in COPD.

We hypothesised airway MAIT cells may be dysregulated in asthma and COPD and contribute to susceptibility to infection.

Methods:

93 adults with asthma, COPD and health underwent phenotyping, sputum induction, phlebotomy, and bronchoscopy. Subgroups underwent trials of inhaled and oral corticosteroids. MAIT cells were analysed by 9-colour flow-cytometry, and Serum vitamin D3 by mass spectrometry.  In vitro monocyte derived macrophages (MDM) were infected with NTHi.

Results:

CD3+TCR-Valpha7.2+CD161+ MAIT cells comprise up to 10% of airway T cells. There was a striking deficiency of MAIT-cells in asthma in blood (P=.005), sputum (P=.002) and biopsies (P=0.02). This deficiency was related to disease severity and chronic treatment with inhaled corticosteroids. Blood MAIT cell frequencies were markedly reduced by 7 days of treatment with oral prednisolone (P=.03), though not inhaled beclometasone. There is significant seasonal variation in MAIT-cell frequencies (R2=0.16, P<0.0001) which is specific to MAIT cells. 28% of the variability in MAIT cell frequencies was attributable to variation in serum vitamin-D3 concentrations.

MAIT cells are also deficient in blood and biopsies (P<.05) in steroid-treated COPD.

In vitro, lung macrophages express MR1. Infection with live NTHi (but not dead NTHi or live influenza virus) induced expression of MR1 on MDM and MAIT cell IFN-γ expression. Corticosteroids reduce bacterially-induced MR1 surface expression and IFN-γ production.

Conclusions:

Airway MAIT cells are numerically and functionally deficient in severe asthma and COPD, likely due to corticosteroids. Whether this deficiency is protective or contributes to immunopathology is unknown, but may contribute to susceptibility to bacterial infection, and to changes in the airway microbiome.