Adiponectin-expressing thymic regulatory T-cells

Abstract

Adiponectin is well-known as an abundant adipokine possessing anti-diabetic, anti- inflammatory, anti-atherogenic and insulin-sensitizing activities. Previous results demonstrate that adiponectin is expressed in a population of regulatory T-cell (Treg) precursors located mainly within the thymic nurse cells (TNC) complexes in thymus. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, glucose and insulin intolerance, as well as fatty liver injuries in wild type mice fed with a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Treatment with the adiponectin-expressing Treg precursors facilitated the maturation of T lymphocytes in the thymus and altered the T-cell repertoire in the peripheral organs. However, adoptive transfer of adiponectin-expressing Treg precursors did not elicit beneficial effects in adiponectin knock out (AKO) mice, largely due to the significantly attenuated development of these cells in thymus of mice without adiponectin. 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. In summary, adiponectin-expressing Treg are critically involved in the selection and development of T lymphocytes within the TNC complexes and represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.