[ASC-list] brisbane AIBN seminar

Jayne Keane jayne.keane at qm.qld.gov.au
Tue Jul 24 06:45:08 UTC 2012



AIBN Special Seminar:



Dr Sandrine Henri, Centre d’Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France


Disentangling DC and macrophage subsets within dermis: from phenotype to function


Wednesday 25 July 2012




AIBN Level 1 Seminar Room



Abstract:  Using knock-in mice (Lang-EGFP-DTR) to track and ablate DCs expressing langerin (CD207) and a combination of three markers, namely CD207, CD11b and CD103, we recently disentangled the dermal DC complexity which contains the following five distinct DC subsets: mLCs, CD207+ CD103-, CD207+ CD103+, CD207- CD11b- and CD207- CD11b+. We also identified their migratory counterparts in draining lymph nodes. 


Using the K5.mOVA model in which membrane OVA (mOVA) is expressed in skin keratinocytes and in the outer root sheath of hair follicle, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset was endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. Using the ALDH assay, we also showed that CD207- CD11b+ DDC subset were uniquely producing retinoic acid and were potent inducers of FoxP3+  dermal subset was heterogeneous, we used a panel of markers and appropriate BM competitive chimera, and validated specific markers allowing us to discriminate monocytes CD11bTregs. As we had evidences that the CD207 derived macrophages from pre-DC-derived CD11b+. Those macrophages are CD64int to high Ly6Clow to high, are CCR2 dependent and showed a low turn over upon BrdU treatment. At steady state, they barely migrate to the CLN but upon inflammation triggering with DNFB they migrate to the draining LN and induce Th1 response. An extensive study allowed us to distinguish different subsets of macrophages within the dermis and we are currently analysing their respective gene expression profile by microarray procedures. We believe that for the first time we provide the finest cartography of DC and macrophage subsets within the skin. As a consequence, vaccine strategy, targeting the skin, will benefit from this recent knowledge. The gene expression analysis of all those subsets will allow us to design new innovative mouse model to further study their respective immune functions in primary and secondary immune responses. 



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