IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation
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IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation. / Yánez, Diana C; Sahni, Hemant; Ross, Susan; Solanki, Anisha; Lau, Ching-In; Papaioannou, Eleftheria; Barbarulo, Alessandro; Powell, Rebecca; Lange, Ulrike C; Adams, David J; Barenco, Martino; Ono, Masahiro; D'Acquisto, Fulvio; Furmanski, Anna L; Crompton, Tessa.
in: EUR J IMMUNOL, Jahrgang 49, Nr. 1, 01.2019, S. 66-78.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation
AU - Yánez, Diana C
AU - Sahni, Hemant
AU - Ross, Susan
AU - Solanki, Anisha
AU - Lau, Ching-In
AU - Papaioannou, Eleftheria
AU - Barbarulo, Alessandro
AU - Powell, Rebecca
AU - Lange, Ulrike C
AU - Adams, David J
AU - Barenco, Martino
AU - Ono, Masahiro
AU - D'Acquisto, Fulvio
AU - Furmanski, Anna L
AU - Crompton, Tessa
N1 - © 2018 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2019/1
Y1 - 2019/1
N2 - The interferon-inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4+ Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild-type (WT) CD4+ T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm-family-deficient CD4+ T cells had higher expression of Th1-associated genes than WT and purified naive Ifitm-family-deficient CD4+ T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm-family-deficient mice, but not Ifitm3-deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL-27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.
AB - The interferon-inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4+ Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild-type (WT) CD4+ T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm-family-deficient CD4+ T cells had higher expression of Th1-associated genes than WT and purified naive Ifitm-family-deficient CD4+ T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm-family-deficient mice, but not Ifitm3-deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL-27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.
KW - Animals
KW - Cell Differentiation/genetics
KW - Cells, Cultured
KW - Hypersensitivity/immunology
KW - Inflammation/immunology
KW - Interferon-gamma/metabolism
KW - Interleukin-27/metabolism
KW - Interleukin-4/metabolism
KW - Lymphocyte Activation/genetics
KW - Membrane Proteins/genetics
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Respiratory System/immunology
KW - Th1 Cells/immunology
KW - Th1-Th2 Balance/genetics
KW - Th2 Cells/immunology
U2 - 10.1002/eji.201847692
DO - 10.1002/eji.201847692
M3 - SCORING: Journal article
C2 - 30365177
VL - 49
SP - 66
EP - 78
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 1
ER -