TY - JOUR
T1 - Classical Flt3L-dependent dendritic cells control immunity to protein vaccine
AU - Anandasabapathy, Niroshana
AU - Feder, Rachel
AU - Mollah, Shamim
AU - Tse, Sze Wah
AU - Longhi, Maria Paula
AU - Mehandru, Saurabh
AU - Matos, Ines
AU - Cheong, Cheolho
AU - Ruane, Darren
AU - Brane, Lucas
AU - Teixeira, Angela
AU - Dobrin, Joseph
AU - Mizenina, Olga
AU - Park, Chae Gyu
AU - Meredith, Matthew
AU - Clausen, Björn E.
AU - Nussenzweig, Michel C.
AU - Steinman, Ralph M.
PY - 2014
Y1 - 2014
N2 - 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 Flt3Ldependent, LN-resident cDCs.
AB - 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 Flt3Ldependent, LN-resident cDCs.
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U2 - 10.1084/jem.20131397
DO - 10.1084/jem.20131397
M3 - Article
C2 - 25135299
AN - SCOPUS:84906568561
SN - 0022-1007
VL - 211
SP - 1875
EP - 1891
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -
