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Cellular sources of iL- 22 binding protein in human ileum

Cellular sources of iL- 22 binding protein in human ileum. Emeric Boisteau Joost Buskermolen Supervisors: R. Josien , J . Martin 18-12-2012. Dysregulation of IL-22. Dysregulation of IL-22 is involved in: Inflammatory bowel diseases (ex: Crohn’s disease) Psoriasis Infection

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Cellular sources of iL- 22 binding protein in human ileum

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  1. Cellular sources of iL-22 binding protein in human ileum EmericBoisteau Joost Buskermolen Supervisors: R. Josien, J. Martin 18-12-2012

  2. Dysregulation of IL-22 Dysregulation of IL-22 is involved in: • Inflammatory bowel diseases (ex: Crohn’s disease) • Psoriasis • Infection The role of IL-22BP regulating IL-22 in vivo is mostly unknown

  3. IL-22 Binding Protein • Soluble and inhibitory receptor for IL-22 • Affinity for IL-22 much higher than IL-22/IL22R • Open questions • Functions during normal and pathological immune responses • Cellular sources

  4. Objectives 1. Identify the cellular sources of IL-22BP in vivo 2. Characterize the regulation of the expression of IL-22BP 3. Understand the role of IL-22BP in inflammatory and auto-immunity pathologies. In human ileum

  5. Preliminary results - IL-22BP • Cellular sources in mice: • Subset of conventional DCs (Martin et al, submitted) • Cells of hematopoietic origin (Nature, 2012) • TCR-β­-, MHCII+ and CD11c+ (Nature, 2012)

  6. Splenic cells Preliminaryresults - IL-22BP sources Martin et al, submitted

  7. Preliminary results - IL-22BP • Cellular sources in mice: • Subset of conventional DCs (Martin et al, submitted) • Cells of hematopoietic origin (Nature, 2012) • TCR-β­-, MHCII+ and CD11c+ (Nature, 2012) • Observations in animal models: • Down-regulation during the peak of damage favours IL-22 protective action (Nature, 2012) • IL-22BP KO mice: increased tumorigenesis in colitis associated models (Nature, 2012)

  8. Materials and methods • Immunofluorescence with confocal microscope • Single staining to test antibodies • Double staining on biopsies of human ileum • Tissue: healthy ileum after intestinal resection • Anti-hIL-22BP • Specific cell markers Co-localization

  9. Cell markers Preliminary

  10. Results • No staining was observed for: • CD4 • CD16 • CD64

  11. CD45+ DAPI CD45 CD45 Merge IL22BP

  12. CD11b+ DAPI CD11b Merge IL22BP

  13. CD3- DAPI CD3 Merge IL22BP

  14. CD8- DAPI CD8 Merge IL22BP

  15. RORγT- DAPI RORγT Merge IL22BP

  16. NKp46- DAPI NKp46 Merge IL22BP

  17. HLA-DR-

  18. Summary • There is a constitutive expression of IL-22BP protein in human intestinal tissue • IL-22BP producingcells in ileumappear to be: • CD45+ • HLA-DR- • CD11b+ • CD3- • CD8- • RORγT- • NKp46- Cells of hematopoietic origin Not APCs Not T cells or NK cells

  19. Discussion • First results of IL-22BP cellular sources in humanin vivo • Theseresultssuggestthat IL-22BP producingcells are not dendriticcells in humanileum • The nature of thesecellsremains to bedetermined • Polymorphonuclearcells (neutrophils, eosinophils)? • Progenitorcells?

  20. Limits of ourwork • Quality of tissue sections • Coupling of the anti-hIL-22BP with Alexa Fluor 568 • Availability and sensitivity of specific cell markers • Competition between anti-hIL-22BP and other antibodies • “Healthy tissues”?

  21. Perspectives • Test more cell markers to fully characterize IL-22BP producing cells • Assess IL-22BP expression in different segments of the gut and other tissues (mesenteric lymph nodes) • Assess IL-22BP expression in human inflammatory bowel diseases (Crohn, UC) • Understand the role of IL-22BP in inflammatory and auto-immune pathologies using a recently developed model of IL-22BP deficient rats

  22. Acknowledgements We are very grateful towards the following persons: • INSERM UMR1064, Center of Research in Transplantation and Immunology, Nantes • Pr. RégisJosien • Dr.Jérome Martin • MichèleHeslan • Laboratoired’Anatomo-Pathologie, CHU Nantes • CélineBossard

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