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Leptin as an immunological adjuvant: enhanced migratory and CD8 + T cell stimulatory capacity of human dendritic cells exposed to leptin
Author(s) -
Mattioli Benedetta,
Straface Elisabetta,
Matarrese Paola,
Quaranta Maria Giovanna,
Giordani Luciana,
Malorni Walter,
Viora Marina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-098095
Subject(s) - leptin , microbiology and biotechnology , cofilin , immune system , leptin receptor , biology , dendritic cell , actin cytoskeleton , chemistry , cytoskeleton , immunology , endocrinology , cell , genetics , obesity
Leptin is an adipocyte‐derived hor‐ mone/cytokine that links nutrition, metabolism, and immune homeostasis and is endowed to modulate several immune responses. We previously demon strated that both immature and mature human den dritic 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 sig naling driving cytoskeleton rearrangement. We found that leptin increases immature DC migratory perfor mance 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 phos phorylation, promotes Rac1 activation. Finally, we found that in immature DCs, leptin up‐regulates inter‐ leukin‐12p70 production on CD40 stimulation and, more importantly, increases their capacity to stimulate activation of autologous CD8 + T cells. Taken alto gether, the findings herein highlight the potential use of leptin as an adjuvant tool in vaccination protocols employing ex vivo‐generated autologous DCs.— Mat‐ tioli, B., Straface, E., Matarrese, P., Quaranta, M. G., Giordani, L., Malorni, W., Viora, M. Leptin as an immunological adjuvant: enhanced migratory and CD8+T cell stimulatory capacity of human dendritic cells exposed to leptin. FASEB J. 22, 2012–2022 (2008)