Leptin selectively augments thymopoiesis in leptin deficiency and lipopolysaccharide-induced thymic atrophy.
The thymus is a lymphoid organ that selects T cells for release to the peripheral immune system. Unfortunately, thymopoiesis is highly susceptible to damage by physiologic stressors and can contribute to immune deficiencies that occur in a variety of clinical settings. No treatment is currently available to protect the thymus from stress-induced involution. Leptin-deficient (ob/ob) mice have severe thymic atrophy and this finding suggests that this hormone is required for normal thymopoiesis. In this study, the ability of leptin to promote thymopoiesis in wild-type C57BL/6 and BALB/c mice, as well as in leptin-deficient (ob/ob) and endotoxin-stressed (Escherichia coli LPS) mice, was determined. Leptin administration induced weight loss and stimulated thymopoiesis in ob/ob mice, but did not stimulate thymopoiesis in wild-type C57BL/6 nor BALB/c mice. In endotoxin-stressed mice, however, leptin prevented LPS-induced thymus weight loss and stimulated TCRalpha gene rearrangement. Coadministration of leptin with LPS blunted endotoxin-induced systemic corticosterone response and production of proinflammatory cytokines. Thus, leptin has a selective thymostimulatory role in settings of leptin deficiency and endotoxin administration, and may be useful for protecting the thymus from damage and augmenting T cell reconstitution in these clinical states.
Hick
Ryan W
RW
Human Vaccine Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Gruver
Amanda L
AL
Ventevogel
Melissa S
MS
Haynes
Barton F
BF
Sempowski
Gregory D
GD
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001284:Atrophy / Q000517:prevention & control; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D013045:Species Specificity; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018836:Inflammation Mediators; D020738:Leptin; D008070:Lipopolysaccharides; D003345:Corticosterone