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ZIB Paper presentation
07.02.2011
Wiebke Ginter
Nuocytes represent a new innate effector leukocytethat mediates type-2 immunityDaniel R. Neill1*, See Heng Wong1*, Agustin Bellosi1*, Robin J. Flynn1, Maria Daly1, Theresa K. A. Langford1,Christine Bucks2, Colleen M. Kane2, Padraic G. Fallon3, Richard Pannell1, Helen E. Jolin1 & Andrew N. J. McKenzie1
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Plays role in helminth infection and asthma Eosinophilia, mucus secretion, IgE production IL-4, IL5, IL-13 Produced by basophils, eosinophils and mast cells Role in Nippostrongylus brasiliensis expulsion unknown
Nippostrongylus brasiliensis
• intestinal nematode of rodents• closely related to the human hookworms (Ancylostoma and
Necator)• infect 740 million people in tropical countries
• N. brasiliensis widely used model for nematode parasites
Maizels, 2003, Nat. Rev. Immunol
Type II immunity and Question
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Type II immunity and Question
IL-13 is critical in immune response to helminths and asthmaWhich cell types to produce this cytokine?
Supp. 1a
Plays role in helminth infection and asthma Eosinophilia, mucus secretion, IgE production IL-4, IL5, IL-13 Produced by basophils, eosinophils and mast cells Role in Nippostrongylus brasiliensis expulsion unknown
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CD4+ splenocytes
Supp.1
Th1 conditions Th2 conditions
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Localisation of eGFP+ cells
Fig. 1c
Supp. 2b
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no T cell
no APC
no gd T cell
no NK/NKT cell
no NK/NKT cell
no DC mono…
no macroph,
granolo
no eosno mast
no pDC
no B cell
Surface markers
Supp. 2a,c
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New cells are no mast, B, T, NK or LTi cells
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Induction of Nuocytes by IL-25 and IL-33
Fig. 1
IL-25 receptor SU of IL-33 receptor
Direct action of these IL
Redundant action
Nuocytes: Lin- eGFP+T1/ST2+IL17BR+
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Presence in imunosurveillance sites
Supp. 4
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Helminth infection
Small intestine
Supp. 2d Fig. 2a
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IL25 and IL33: partially redundant roles
Il17br-/- Il1rl1-/- IL17br-/-
Il1rl1-/-
No IL25R No SU IL33R
No IL25R, IL33R
Fig.2
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Nuocyte Cultures
Fig. 3
IL33 and IL7 needed for expansion Most cell surface markers maintained Did not differentiate
Supp. 8
Nuocytes: Lin- ICOS+T1/ST2+IL17BR+IL-7Rα+
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Cytokine profile
Fig. 3Supp. 9
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Adoptive transfer of cultured nuocytes into Il17br-/- mice restores an IL25-responsive phenotype
Il17br-/-
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Restoring protective IR in IL17BR-/- mice
Fig. 4
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IL13 of nuocytes is necessary and sufficient for worm expulsion
Fig. 4IL13 from nuocytes is the only important source
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Dialogue between T cells and nuocytes
Fig. 4
T cells Nuocytes
Enhance cytokines, augment resp
Maintain: expansion survival
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Summary
• new class of cells: Nuocytes
• important for the type-2 immunity: protection from parasitic helminths
• release of type II cytokines, activating eosinophiles and goblet cells and secreting mucus and IgE
• Key source of IL-13 release during early steps of helminth infection
• Expand rapidly in response to IL-25 and IL-33 (type-2 initiators)
• Lack: nuocytes expansion ↓, defect in worm expulsion
• present in immunosurveillance sites
• Secrete high levels of IL13 and IL5
• Enhance T cell responses
• highly specialized type type-2 regulatory cells
• New possible target for immune modulation? Asthma treatment?
T cells Nuocytes
Enhance cytokines, augment resp
Maintain: expansion survival
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Supplementary
Saenz, 2010, Trends in Immunology
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no T cell
no APC
no gd T cell
no NK/NKT cell
no NK/NKT cell
no DC mono…
no macroph, granolo
no eosno mast
no pDC
no B cell
Surface markers
Supp. 2a,c
21DR Neill et al. Nature 000, 1-4 (2010) doi:10.1038/nature08900
Adoptive transfer of wild-type nuocytes, but not IL13-deficient nuocytes, restores rapid worm expulsion in N. brasiliensis-infected Il17br
_/_ mice.
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