Abstract
Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Results of the present study demonstrate that adiponectin is expressed in a population of regulatory T-cells (Treg) resided within the thymic nurse cell (TNC) complexes. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, improved glucose and insulin tolerance, prevented fatty liver injuries in wild-type mice fed a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. In summary, adiponectin plays an important role in the selection and development of T lymphocytes within the TNC complexes. Adiponectin-expressing Treg represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.
Highlights
Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases
In situ hybridization revealed that most of the cells containing the mRNA transcript of ADIPOQ were located within the lymphoepithelial cell clusters (Fig. 1c), which were positively stained with antibodies against cytokeratin 5 and/or cytokeratin 8 (Fig. 1d), markers of the thymic nurse cell (TNC) complexes[28]
In contrast to the ADIPOQ transcript, which was present in only a few individual cells (Fig. 1c), adiponectin protein was widely distributed in the extracellular space between the thymocytes and the cage-like structures formed by the epithelial plasma membrane of the TNC complexes (Fig. 1d)
Summary
Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. 1234567890():,; Adiponectin is a well-known circulating glyco-hormone regulating energy metabolism and immune homeostasis[1] It possesses potent anti-inflammatory, anti-diabetic, and anti-tumorigenic activities[2,3,4]. In the presence of stromal cells, adiponectin selectively inhibits lymphopoiesis in long-term cultures of bone marrow or those initiated with lymphocyte precursors[23]. Deficiency of adiponectin alters the maturation of Treg and the selection of T lymphocytes in thymus, facilitating the development of diseases such as breast cancer and obesity-related metabolic complications
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
