Tissue Eng Regen Med.  2019 Oct;16(5):539-548. 10.1007/s13770-019-00205-y.

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

• Kang TH
• Park JH
• Shin D
• Choi H
• Kim J
• Lee MC

• KMID: 2464073
• DOI: http://doi.org/10.1007/s13770-019-00205-y

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 (T(reg)) 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 T(regs) (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 T(reg) expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of T(regs). However, a decrease in T(regs) 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 T(reg) expression when they are cultured with splenocytes. Of note, brown adipocytes maintained T(reg) 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.

Keyword

Brown adipocyte; Negative pressure; Regulatory T cell; Splenocyte

MeSH Terms

Adipocytes
Adipocytes, Brown*
Adipocytes, White
Animals
Coculture Techniques*
Cytokines
Humans
Infant, Newborn
Interleukin-10
Ligands
Mice
Necrosis
Cytokines
Interleukin-10
Ligands