IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4.
Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic infection and allergic disorders. CD4(+) T cells which produce type 2 cytokines can be generated via IL-4-dependent and -independent pathways. Although the IL-4-dependent pathway is well documented, factors that drive IL-4-independent Th2 cell differentiation remain obscure. We report here that the new cytokine IL-33, in the presence of Ag, polarizes murine and human naive CD4(+) T cells into a population of T cells which produce mainly IL-5 but not IL-4. This polarization requires IL-1R-related molecule and MyD88 but not IL-4 or STAT6. The IL-33-induced T cell differentiation is also dependent on the phosphorylation of MAPKs and NF-kappaB but not the induction of GATA3 or T-bet. In vivo, ST2(-/-) mice developed attenuated airway inflammation and IL-5 production in a murine model of asthma. Conversely, IL-33 administration induced the IL-5-producing T cells and exacerbated allergen-induced airway inflammation in wild-type as well as IL-4(-/-) mice. Finally, adoptive transfer of IL-33-polarized IL-5(+)IL-4(-)T cells triggered airway inflammation in naive IL-4(-/-) mice. Thus, we demonstrate here that, in the presence of Ag, IL-33 induces IL-5-producing T cells and promotes airway inflammation independent of IL-4.
Kurowska-Stolarska
Mariola
M
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow United Kingdom.
Kewin
Pete
P
Murphy
Grace
G
Russo
Remo C
RC
Stolarski
Bartosz
B
Garcia
Cristiana Couto
CC
Komai-Koma
Mousa
M
Pitman
Nick
N
Li
Yubin
Y
Niedbala
Wanda
W
McKenzie
Andrew N J
AN
Teixeira
Mauro M
MM
Liew
Foo Y
FY
Xu
Damo
D
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology; D007371:Interferon-gamma / Q000172:deficiency; D018793:Interleukin-13 / Q000096:biosynthesis; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis*; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D000485:Allergens; D017252:CD3 Complex; D018984:Epitopes, T-Lymphocyte; C506536:IL33 protein, human; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin