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Immunity. 2015 Aug 18;43(2):318-30. doi: 10.1016/j.immuni.2015.07.015.

Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites.

Author information

1
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm 171 77, Sweden. Electronic address: jonathan.coquet@ki.se.
2
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium.
3
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; School of Medicine, University of Queensland, Herston, QLD 4006, Australia.
4
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Biomedical Molecular Biology, Gent University, Gent 9000, Belgium.
5
Bioceros, Utrecht 3584CM, the Netherlands.
6
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm 171 77, Sweden.
7
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
8
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Respiratory Medicine, Gent University Hospital, Gent 9000, Belgium.
9
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Respiratory Medicine, Gent University Hospital, Gent 9000, Belgium; Department of Pulmonary Medicine, ErasmusMC, Rotterdam 3015CD, the Netherlands.

Abstract

Asthma is a T helper 2 (Th2)-cell-mediated disease; however, recent findings implicate Th17 and innate lymphoid cells also in regulating airway inflammation. Herein, we have demonstrated profound interleukin-21 (IL-21) production after house dust mite (HDM)-driven asthma by using T cell receptor (TCR) transgenic mice reactive to Dermatophagoides pteronyssinus 1 and an IL-21GFP reporter mouse. IL-21-producing cells in the mediastinal lymph node (mLN) bore characteristics of T follicular helper (Tfh) cells, whereas IL-21(+) cells in the lung did not express CXCR5 (a chemokine receptor expressed by Tfh cells) and were distinct from effector Th2 or Th17 cells. Il21r(-/-) mice developed reduced type 2 responses and the IL-21 receptor (IL-21R) enhanced Th2 cell function in a cell-intrinsic manner. Finally, administration of recombinant IL-21 and IL-25 synergistically promoted airway eosinophilia primarily via effects on CD4(+) lymphocytes. This highlights an important Th2-cell-amplifying function of IL-21-producing CD4(+) T cells in allergic airway inflammation.

PMID:
26287681
DOI:
10.1016/j.immuni.2015.07.015
[Indexed for MEDLINE]
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