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.


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*


  • 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