Impairment of dendritic cell functionality and steady-state number in obese mice.
There is a finely tuned interplay between immune and neuroendocrine systems. Metabolic disturbances like obesity will have serious consequences on immunity both at the cellular and at the cytokine expression levels. Our in vivo results confirm the immune deficiency of ob/ob mice, leptin deficient and massively obese, characterized by a reduced Ag-specific T cell proliferation after keyhole limpet hemocyanin immunization. In this report, we show that dendritic cells (DCs), major APCs involved in T lymphocyte priming, are affected in obese mice. Both their function and their steady-state number are disturbed. We demonstrate that DCs from ob/ob mice are less potent in stimulation of allogenic T cells in vitro. This impaired functionality is not associated with altered expression of phenotypic markers but with the secretion of immunosuppressive cytokines such as TGF-beta. Moreover, we show increased in vivo steady-state number of epidermal DCs in ob/ob mice, which is not due to a migratory defect. The ob/ob mice are characterized by the absence of functional leptin, a key adipokine linking nutrition, metabolism, and immune functions. Interestingly, intradermal injection of leptin is able to restore epidermal DC number in obese mice. Thus, DCs might be directly sensitive to metabolic disturbances, providing a partial explanation of the immunodeficiency associated with obesity.
Macia
Laurence
L
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8527, Institut de Biologie de Lille/Institut Pasteur de Lille, 1 Rue Albert Calmette, 59019 Lille cedex, France.
Delacre
Myriam
M
Abboud
Georges
G
Ouk
Tan-Sothéa
TS
Delanoye
Anne
A
Verwaerde
Claudie
C
Saule
Pasquine
P
Wolowczuk
Isabelle
I
D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology* / Q000473:pathology; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D020738:Leptin / Q000172:deficiency* / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D020738:Leptin; D016212:Transforming Growth Factor beta