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RESEARCH PRODUCT
Classical Flt3L-dependent dendritic cells control immunity to protein vaccine
Lucas BraneChae Gyu ParkMatthew M. MeredithAngela TeixeiraJoseph S. DobrinCheolho CheongS. MollahMaria Paula LonghiSze Wah TseInes MatosRachel E. FederBjörn E. ClausenMichel C. NussenzweigSaurabh MehandruRalph M. SteinmanOlga MizeninaNiroshana AnandasabapathyDarren Ruanesubject
MaleCellular immunityInjections IntradermalLangerinOvalbuminInjections SubcutaneousT cellImmunologyAntigen presentationGene ExpressionPriming (immunology)Mice Transgenicchemical and pharmacologic phenomenaLigandsInterferon-gammaMice03 medical and health sciences0302 clinical medicineAntigenT-Lymphocyte SubsetsImmunitymedicineAnimalsHumansImmunology and AllergyLectins C-Type030304 developmental biologyMice KnockoutAntigen PresentationVaccines0303 health sciencesbiologyMembrane ProteinsProteinsDendritic Cellsbiochemical phenomena metabolism and nutritionImmunity Humoral3. Good healthMice Inbred C57BLMannose-Binding Lectinsmedicine.anatomical_structureAntigens SurfaceHumoral immunityImmunologybiology.proteinbacteriaFemaleTranscription Factors030215 immunologydescription
DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin+ DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-08-18 | Journal of Experimental Medicine |