TY - JOUR
T1 - NLRP6 negatively regulates type 2 immune responses in mice
AU - Chenuet, Pauline
AU - Marquant, Quentin
AU - Fauconnier, Louis
AU - Youness, Ali
AU - Mellier, Manon
AU - Marchiol, Tiffany
AU - Rouxel, Nathalie
AU - Messaoud-Nacer, Yasmine
AU - Maillet, Isabelle
AU - Ledru, Aurélie
AU - Quesniaux, Valérie F J
AU - Ryffel, Bernhard
AU - Horsnell, William
AU - Végran, Frédérique
AU - Apetoh, Lionel
AU - Togbe, Dieudonnée
N1 - © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2022/5/25
Y1 - 2022/5/25
N2 - BACKGROUND: Inflammasomes are large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection. Following activation, inflammasomes trigger cell death and the release of biological active forms of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome is required for IL-18 secretion by intestinal epithelial cells, macrophages and T cells, contributing to homeostasis and self-defense against pathogenic microbes. However, the involvement of NLRP6 in type 2 lung inflammation remains elusive.METHODS: Wild type (WT) and Nlrp6-/- mice were used. Birch pollen extract (BPE) induced allergic lung inflammation, eosinophil recruitment, Th2 related cytokine and chemokine production, airway hyperresponsiveness and lung histopathology, Th2 cell differentiation, GATA3 and Th2 cytokines expression, were determined. Nippostrongylus brasiliensis (Nb) infection, worm count in intestine, type 2 innate lymphoid cell (ILC2) and Th2 cells in lungs were evaluated.RESULTS: We demonstrate in Nlrp6-/- mice that a mixed Th2/Th17 immune responses prevailed following birch pollen challenge with increased eosinophils, ILC2, Th2 and Th17 cell induction and reduced IL-18 production. Nippostrongylus brasiliensis infected Nlrp6-/- mice featured enhanced early expulsion of the parasite due to enhanced type 2 immune responses compared to WT hosts. In vitro, NLRP6 repressed Th2 polarization, as shown by increased Th2 cytokines and higher expression of the transcription factor GATA3 in the absence of NLRP6. Exogenous IL-18 administration partially reduced the enhanced airways inflammation in Nlrp6-/- mice.CONCLUSIONS: In summary, our data identify NLRP6 as a negative regulator of type 2 immune responses.
AB - BACKGROUND: Inflammasomes are large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection. Following activation, inflammasomes trigger cell death and the release of biological active forms of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome is required for IL-18 secretion by intestinal epithelial cells, macrophages and T cells, contributing to homeostasis and self-defense against pathogenic microbes. However, the involvement of NLRP6 in type 2 lung inflammation remains elusive.METHODS: Wild type (WT) and Nlrp6-/- mice were used. Birch pollen extract (BPE) induced allergic lung inflammation, eosinophil recruitment, Th2 related cytokine and chemokine production, airway hyperresponsiveness and lung histopathology, Th2 cell differentiation, GATA3 and Th2 cytokines expression, were determined. Nippostrongylus brasiliensis (Nb) infection, worm count in intestine, type 2 innate lymphoid cell (ILC2) and Th2 cells in lungs were evaluated.RESULTS: We demonstrate in Nlrp6-/- mice that a mixed Th2/Th17 immune responses prevailed following birch pollen challenge with increased eosinophils, ILC2, Th2 and Th17 cell induction and reduced IL-18 production. Nippostrongylus brasiliensis infected Nlrp6-/- mice featured enhanced early expulsion of the parasite due to enhanced type 2 immune responses compared to WT hosts. In vitro, NLRP6 repressed Th2 polarization, as shown by increased Th2 cytokines and higher expression of the transcription factor GATA3 in the absence of NLRP6. Exogenous IL-18 administration partially reduced the enhanced airways inflammation in Nlrp6-/- mice.CONCLUSIONS: In summary, our data identify NLRP6 as a negative regulator of type 2 immune responses.
KW - CD4+ T cells
KW - GATA3
KW - ILC2
KW - IL‐18
KW - NLRP6
KW - Nippostrongylus brasiliensis
KW - Th17
KW - Th2
KW - allergic asthma
KW - birch pollen
KW - inflammasome
UR - http://www.scopus.com/inward/record.url?scp=85131522119&partnerID=8YFLogxK
U2 - 10.1111/all.15388
DO - 10.1111/all.15388
M3 - Article
C2 - 35615773
SN - 0105-4538
JO - Allergy
JF - Allergy
ER -