IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.
Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell-mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4-independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
Wang
Yui-Hsi
YH
Department of Immunology and Center of Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Angkasekwinai
Pornpimon
P
Lu
Ning
N
Voo
Kui Shin
KS
Arima
Kazuhiko
K
Hanabuchi
Shino
S
Hippe
Andreas
A
Corrigan
Chris J
CJ
Dong
Chen
C
Homey
Bernhard
B
Yao
Zhengbin
Z
Ying
Sun
S
Huston
David P
DP
Liu
Yong-Jun
YJ
D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D007107:Immune System; D007156:Immunologic Memory; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C486701:IL25 protein, human; D020381:Interleukin-17; C495607:MAF protein, human; D016755:Proto-Oncogene Proteins c-jun; D051257:Proto-Oncogene Proteins c-maf; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin