Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin.
Leptin is an adipocyte-derived hormone/cytokine that links nutrition, metabolism, and immune homeostasis and is endowed to modulate several immune responses. We previously demonstrated that both immature and mature human dendritic cells (DCs) express a functional leptin receptor, and we found that leptin activates DCs, licenses them for Th1 priming, and promotes DC survival. Moreover, we found that leptin induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. Here we monitor the effects of leptin on DC migratory capacities, focusing on the intracellular signaling driving cytoskeleton rearrangement. We found that leptin increases immature DC migratory performance both by favoring cytoskeleton dynamics and by up-regulating CCR7 surface expression, thus favoring chemotactic responsiveness. We found that in immature DCs, leptin activates cofilin, favoring the turnover of actin microfilaments, and, by triggering Vav phosphorylation, promotes Rac1 activation. Finally, we found that in immature DCs, leptin up-regulates interleukin-12p70 production on CD40 stimulation and, more importantly, increases their capacity to stimulate activation of autologous CD8(+) T cells. Taken altogether, the findings herein highlight the potential use of leptin as an adjuvant tool in vaccination protocols employing ex vivo-generated autologous DCs.
Mattioli
Benedetta
B
Department of Drug Research and Evaluation, Istituto Superiore di Sanità, 299 Viale Regina Elena, 00161 Rome, Italy.
Straface
Elisabetta
E
Matarrese
Paola
P
Quaranta
Maria Giovanna
MG
Giordani
Luciana
L
Malorni
Walter
W
Viora
Marina
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D015398:Signal Transduction
D000276:Adjuvants, Immunologic; D020738:Leptin