Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites.
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.
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.
Jonathan M
JM
Coquet
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium.
Martijn J
MJ
Schuijs
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.
Mark J
MJ
Smyth
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium.
Kim
K
Deswarte
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Biomedical Molecular Biology, Gent University, Gent 9000, Belgium.
Rudi
R
Beyaert
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Biomedical Molecular Biology, Gent University, Gent 9000, Belgium.
Harald
H
Braun
Bioceros, Utrecht 3584CM, the Netherlands.
Louis
L
Boon
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm 171 77, Sweden.
Gunilla B
GB
Karlsson Hedestam
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.
Steven L
SL
Nutt
VIB Inflammation Research Center (IRC), Gent University, Zwijnaarde 9052B, Belgium; Department of Respiratory Medicine, Gent University Hospital, Gent 9000, Belgium.
Hamida
H
Hammad
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.
Bart N
BN
Lambrecht
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D007111:Immunity, Cellular; D007378:Interleukins / Q000008:administration & dosage; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D054380:Receptors, CXCR5 / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000008:administration & dosage* / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C513179:CXCR5 protein, mouse; D007378:Interleukins; C442281:Mydgf protein, mouse; D011948:Receptors, Antigen, T-Cell; D054380:Receptors, CXCR5; D053655:Receptors, Interleukin-21; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1