Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions

Abstract

Background:Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (Treg) expression under intermittent hypobaric conditions.Methods:Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of Tregs (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined.Results:Splenocytes, cultured with brown and white adipocytes, exhibited comparable Treg expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of Tregs. However, a decrease in Tregs was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions.Conclusion:Both brown and white adipocytes support Treg expression when they are cultured with splenocytes. Of note, brown adipocytes maintained Treg expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.

A Therapeutic Nanovaccine that Generates Anti‐Amyloid Antibodies and Amyloid‐specific Regulatory T Cells for Alzheimer's Disease

“…[ 13 ] Treg cells are a subset of CD4 + T cells that express Foxp3, which is thought to be essential for Treg cell efficacy. [ 14 ] Treg cells can attenuate neuroinflammation in AD by secreting anti‐inflammatory cytokines such as transforming growth factor‐β (TGF‐β) and interleukin (IL)‐10. The adoptive transfer of Treg cells to AD mice results in a decrease in Aβ plaques and improved cognitive function.…”