Human basophils interact with memory T cells to augment Th17 responses.
Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.
Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC.
Keiko
K
Wakahara
Nobuyasu
N
Baba
Vu Quang
VQ
Van
Philippe
P
Bégin
Manuel
M
Rubio
Pasquale
P
Ferraro
Benoît
B
Panzini
Ramses
R
Wassef
Raymond
R
Lahaie
Yves
Y
Caussignac
Raja
R
Tamaz
Carole
C
Richard
Geneviève
G
Soucy
Guy
G
Delespesse
Marika
M
Sarfati
D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006632:Histamine / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007377:Interleukin-3 / Q000276:immunology / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
C506536:IL33 protein, human; D020381:Interleukin-17; D007377:Interleukin-3; D000067596:Interleukin-33; D007378:Interleukins; D011970:Receptors, Histamine H2; D006632:Histamine; D007371:Interferon-gamma