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Marius Döring ZIB Class of 2009 paper presentation 14.02.2011

Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells.

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Marius Döring ZIB Class of 2009 paper presentation 14.02.2011

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  1. Immobilizedchemokinefieldsand soluble chemokinegradientscooperativelyshapemigrationpatternsofdendriticcells Kathrin Schumann, Tim Lämmermann,Markus Bruckner,Daniel F. Legler, Julien Polleux, Joachim P. Spatz,Gerold Schuler, Reinhold Förster, Manfred B. Lutz, Lydia Sorokin, and Michael Sixt Marius Döring ZIB Class of 2009 paper presentation 14.02.2011

  2. Introduction Chemokines: • chemotactic cytokines • Small 8-10 kDa • classification according to positioning of 4 cysteine residues • signal via GPCR • central orchestrators of hematopoetic system • Homing & positioning of lymphocytes in secondary lymphoid organs • Integrin activation • Polarization of actomyosin cytoskeleton

  3. Introduction Cell movement on a surface: • Haptokinesis vs haptotaxis adhesion independent: • chemokinesis va chemotaxis Chemotaxis Haptokinesis Haptotaxis biased by chemotactic gradient

  4. Model system: Migration of DC depentent on CCR7 and its ligands CCL19/21 CCL19: mostly soluble due to truncated N-terminus CCL21: binds to heperansulfate Adopted from Rot et. al 2008

  5. Results LPS matured DC on unfixed cryosection of inguinal LN DCs mirgate on LN intothe T cellareaalongtheinterfollicularregion

  6. Results DCs mirgate on LN in a CCR7 & CCR7 liganddependentmanneralong a soluble gradient

  7. Results • Immobilized CCL21 triggers: • rapid spreading • randommigration • releaseof soluble factortoattractother DCs

  8. Results DCs generate a truncated CCL21 upon encouterof CCL21 bycleavagefromthe C terminus

  9. Results Haptokinesis (spreading, polarization & migration) of DCs isinducedbyinteractionof CCR7 andimmobilized ß2 integrin

  10. Results Chemotacticandadhesivesignalscompete& thosetwoforcesleadto a directedhaptotacticmovement

  11. Conclusion • Mature DCs activated ß2 integrinandcytoskeletalpolarization upon contactwithimmonilized CCL21  haptokineticmovement • CCL19 did not induceadhesion but cellularpolarization chemotacticmovement • CombinationofCCL19/21 leadtodirectionallybiasedhaptokineticmigration • Duringtheirmirgation DCs generated a truncatedversionof CCL21 • Immobiliezd CCL21 dictatesthe PW • Soluble factorsdirectionofmigration

  12. The End !!!Thank you for your attention!!! ??Question??

  13. Introduction

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