Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites
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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.
Original language | English |
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Journal | Immunity |
Volume | 43 |
Issue number | 2 |
Pages (from-to) | 318-30 |
Number of pages | 13 |
ISSN | 1074-7613 |
DOIs | |
Publication status | Published - 18 Aug 2015 |
Bibliographical note
Copyright © 2015 Elsevier Inc. All rights reserved.
- Animals, Antigens, Dermatophagoides/immunology, Arthropod Proteins/immunology, Asthma/immunology, CD4-Positive T-Lymphocytes/immunology, Cells, Cultured, Cysteine Endopeptidases/immunology, Eosinophilia/immunology, Eosinophils/drug effects, 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, Th2 Cells/immunology
Research areas
ID: 356968852