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

Jonathan M Coquet; Martijn J Schuijs; Mark J Smyth; Kim Deswarte; Rudi Beyaert; Harald Braun; Louis Boon; Gunilla B Karlsson Hedestam; Steven L Nutt; Hamida Hammad; Bart N Lambrecht

doi:10.1016/j.immuni.2015.07.015

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

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

Authors

Affiliations

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.

PMID: 26287681
DOI: 10.1016/j.immuni.2015.07.015

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Dermatophagoides / immunology
Arthropod Proteins / immunology
Asthma / immunology*
CD4-Positive T-Lymphocytes / immunology*
Cells, Cultured
Cysteine Endopeptidases / immunology
Eosinophilia / immunology*
Eosinophils / drug effects*
Eosinophils / immunology
Immunity, Cellular
Interleukins / administration & dosage
Lung / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Pyroglyphidae / immunology
Receptors, Antigen, T-Cell / genetics
Receptors, CXCR5 / metabolism
Receptors, Interleukin-21 / administration & dosage*
Receptors, Interleukin-21 / genetics
Th2 Cells / immunology*

Substances

Antigens, Dermatophagoides
Arthropod Proteins
CXCR5 protein, mouse
Interleukins
Mydgf protein, mouse
Receptors, Antigen, T-Cell
Receptors, CXCR5
Receptors, Interleukin-21
Cysteine Endopeptidases
Dermatophagoides pteronyssinus antigen p 1

Associated data

GEO/GSE72005