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Intrathymic Role for Leptin in the Prevention of Thymic Atrophy
Author(s) -
Gruver Amanda Louise,
Sempowski Gregory D
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/fasebj.22.1_supplement.845.4
Subject(s) - leptin , endocrinology , medicine , leptin receptor , cd8 , atrophy , inflammation , immune system , cytokine , lipopolysaccharide , stat , biology , immunology , signal transduction , stat3 , obesity , microbiology and biotechnology
Thymic atrophy is highly inducible by stress. Prolonged thymus atrophy can contribute to T cell deficiency or prevent immune recovery after acute T cell depletion, to which no treatment is currently available. Leptin is an endogenous metabolic hormone used therapeutically for obesity. We have shown that leptin induces thymopoiesis during lipopolysaccharide (LPS) induced stress by increasing thymus weight and TCR gene rearrangement. We have also shown that leptin blunts corticosteroid and pro‐inflammatory cytokine responses to LPS. The role of leptin within the thymus however is currently unknown. We now report that the leptin receptor predominantly co‐localizes to thymic medulla, with long and short isoforms being expressed. We further demonstrated that leptin protects against LPS‐induced apoptosis of CD4+CD8+ DP thymocytes and increases proliferation in CD4−CD8− DN thymocytes. Alternatively, we evaluated the endotoxin response in the absence of leptin or its receptor. We found that LPS induced substantial thymic atrophy in leptin deficient ob/ob mice while only induced mild thymic atrophy in leptin receptor deficient db/db mice. Both ob/ob and db/db mice had severely reduced cytokine responses to LPS, suggesting duel anti‐ vs pro‐inflammatory roles of leptin. Taken together, these data strongly suggest multiple roles of leptin in modulating thymopoiesis and inflammation. Supported by AG025150.