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

JM Coquet, MJ Schuijs, MJ Smyth, K Deswarte, R Beyaert, H Braun, L Boon, GBK Hedestam, SL Nutt, H Hammad, Bart Lambrecht

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104 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)318-330
Number of pages13
JournalImmunity
Volume43
Issue number2
DOIs
Publication statusPublished - 2015

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