1 / 21

ZIB Paper presentation 07.02.2011 Wiebke Ginter

Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity Daniel R. Neill1*, See Heng Wong1*, Agustin Bellosi1*, Robin J. Flynn1, Maria Daly1, Theresa K. A. Langford1,

ardith
Download Presentation

ZIB Paper presentation 07.02.2011 Wiebke Ginter

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity Daniel 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 ZIB Paper presentation 07.02.2011 Wiebke Ginter

  2. Type II immunity and Question • 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

  3. Type II immunity and Question • 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 IL-13 is critical in immune response to helminths and asthma Which cell types to produce this cytokine? Supp. 1a

  4. CD4+ splenocytes Th1 conditions Th2 conditions Supp.1

  5. Localisation of eGFP+ cells Fig. 1c Supp. 2b

  6. Surface markers no NK/NKT cell no NK/NKT cell no DC mono… no APC no gd T cell no T cell no eos no macroph, granolo no mast no pDC no B cell Supp. 2a,c

  7. New cells are no mast, B, T, NK or LTi cells

  8. Induction of Nuocytes by IL-25 and IL-33 Nuocytes: Lin- eGFP+T1/ST2+IL17BR+ Fig. 1 IL-25 receptor SU of IL-33 receptor  Redundant action  Direct action of these IL

  9. Presence in imunosurveillance sites Supp. 4

  10. Helminth infection Small intestine Fig. 2a Supp. 2d

  11. IL25 and IL33: partially redundant roles Fig.2

  12. 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+

  13. Cytokine profile Fig. 3 Supp. 9

  14. Adoptive transfer of cultured nuocytes into Il17br-/-mice restores an IL25-responsive phenotype Il17br-/-

  15. Restoring protective IR in IL17BR-/- mice Fig. 4

  16. IL13 of nuocytes is necessary and sufficient for worm expulsion IL13 from nuocytes is the only important source Fig. 4

  17. Enhance cytokines, augment resp T cells Nuocytes Maintain: expansion survival Dialogue between T cells and nuocytes Fig. 4

  18. Enhance cytokines, augment resp T cells Nuocytes Maintain: expansion survival 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?

  19. Supplementary Saenz, 2010, Trends in Immunology

  20. Surface markers no NK/NKT cell no NK/NKT cell no T cell no APC no DC mono… no gd T cell no macroph, granolo no eos no pDC no B cell no mast Supp. 2a,c

  21. Adoptive transfer of wild-type nuocytes, but not IL13-deficient nuocytes, restores rapid worm expulsion in N. brasiliensis-infected Il17br_/_ mice. DR Neill et al. Nature000, 1-4 (2010) doi:10.1038/nature08900

More Related