Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

Abstract

Protective immunity to protein vaccines is controlled by Flt3L-dependent classical LN-resident dendritic cells, and dampened by migratory dendritic cells.

Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells

“…Homeostasis of DCs is therefore paramount for induction of effective immunity to microbes as well as maintenance of immune tolerance to selfantigens. For example, removal of DCs abrogates the initiation of immune responses to exogenous antigens (1,2). Conversely, perturbation of the DC compartment by prolonging DC survival in the mouse leads to autoimmunity (3,4).…”

“…Conversely, pDCs express TLR-7 and abundant type 1 interferons but lack the ability to present antigen in noninflammatory conditions (7,8). pDCs have been implicated in the pathogenesis of systemic lupus erythematosus (9,10), whereas cDCs are critical for activating killer T cells (CTLs) against Listeria and Plasmodia (1) and immune responses to proteinaceous vaccines (2). The DC subsets have different lifespans (11,12).…”

Duality at the gate: Skin dendritic cells as mediators of vaccine immunity and tolerance

“…45 We and others have observed that skin DCs (in the steady state) are transcriptionally far more closely related to each other than to their LN resident counterparts. 28,46,47 This finding was initially surprising, as some skin and LN populations share both common precursors, as well as a capacity for functionally similar properties, such as cross-presentation. Furthermore, even LCs are more closely related to the other skin DC populations, 28 despite arising from a unique developmental pathway, more akin to monocytes and microglia than the remaining skin resident DCs.…”

“…Furthermore, even LCs are more closely related to the other skin DC populations, 28 despite arising from a unique developmental pathway, more akin to monocytes and microglia than the remaining skin resident DCs. 48,49 Moreover, skin DC in the steady-state and during Flt3L treatment maintain a transcriptional signature that is both mature as well as tolerogenic, 28,46 while lymphoid resident DC tend to selectively express these markers during maturation, highlighting broad programming differences between these 2 groups.…”

“…92 Recently, we demonstrated that combining DEC205-targeted antigen with adjuvant and Flt3L treatment (to expand DC) can further amplify the resulting immune response. 46 However, in the absence of an adjuvant to mature or license DC, DEC205 targeting generates immune tolerance. In a murine model of multiple sclerosis (Experimental Autoimmune Encephalitis), DEC205 fused to Myelin Oligodendrocyte Gylcoprotein (MOG) was able to prevent and ameliorate the disease phenotype.…”