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Melanocortin signaling via the MC4 receptor regulates T cell function
Author(s) -
Youm YunHee,
Yang Hyunwon,
Butler Andrew,
Dixit Vishwa Deep
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.843.11
Subject(s) - melanocortin , thymic involution , biology , lymphopoiesis , immune system , medicine , endocrinology , melanocortin 4 receptor , receptor , t cell , microbiology and biotechnology , haematopoiesis , immunology , stem cell , genetics , hormone
The central melanocortin pathway is critical for regulating food intake and energy expenditure. However, precise role of melanocortins and MC4 receptor in regulation of thymic function remains to be elucidated. Here we demonstrate that MC4R are highly expressed in thymus and lymphoid organs. Compared to wild type control mice, genetic deletion of MC4R led to reduced cellularity and loss of cortico‐medullary junctions suggesting increased thymic involution. Interestingly, the absence of MC4R mediated signals caused a marked increase in lipid bearing thymic fibroblasts and reduction in medullary thymic epithelial cells with reduced thymic output. Analysis of lymphoid progenitors revealed significant reduction in LSK cells in bone marrow and ETP cells in thymus. Using complementarity determining region 3 (CDR3) length polymorphism analysis we next demonstrated that absence of MC4R causes a severe contraction of peripheral T cell receptor diversity suggesting reduced immune‐surveillance. Collectively, these data demonstrates a novel role of melanocortin ‐MC4R pathway in coupling metabolic and immune system. In addition, our findings suggest that specific Mc4R agonists may serve as an important target for rejuvenating thymic function.