Adiponectin-expressing Treg facilitate T lymphocyte development in thymic nurse cell complexes

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.

Emerging Roles of Adipose Tissue in the Pathogenesis of Psoriasis and Atopic Dermatitis in Obesity

“…In contrast to the blood levels of other adipokines, blood adiponectin levels are decreased in obesity ( Hafidi et al., 2019 ) and have been shown to be decreased in patients with PSO ( Kyriakou et al., 2017 ; Li et al., 2014 ). Primarily recognized as a metabolic mediator of insulin sensitivity, adiponectin also exerts anti-inflammatory properties by inhibiting the activation of KCs, macrophages, and T cells ( Li et al., 2019 ; Zhang et al., 2021b ). In vitro, adiponectin suppresses IL-6, TNF-α, and IL-12 production from activated macrophages and IL-6 production of KCs, and it inhibits the IL-1β/IL-23‒mediated production of IL-17 in dermal γδ T cells ( Shibata et al., 2015 , 2011 ).…”

Thymic involution caused by repeated cocaine administration includes apoptotic cell loss followed by ectopic adipogenesis

“…Since the circulating levels of adiponectin were unchanged between the control and cocaine groups (Fig 5E ), the downregulation of adiponectin to occur locally in the microenvironment of the thymus. It has been reported that lymphocytes [38] as well as certain other cells within thymus [39] express the AdipoQ gene. However, given the limited expression of AdipoQ in these cells as well as the fact that AdipoQ is highly abundant in circulation, severe and apparent decrease in AdipoQ as observed by immunoblot and histochemistry, respectively, may be attributable to a loss of this protein in the extracellular microenvironment PLOS ONE of the thymus.…”

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency

“…Lack of APN increases T cells activation with the reduction of Treg that exacerbates the severity of the disease [56]. Furthermore, APN is essential for T cell development in thymus ( Zhang et al, 2021 ). as A result, low APN due to SARS-CoV-2-induced adipose tissue dysfunction and production from T lymphocytes may enhance inflammatory reaction and development of lymphopenia in a vicious cycle.…”