Differentiated all-trans retinoic acid response of naive CD4+CD25-cells isolated from rats with collagen-induced arthritis and healthy ones under in vitro conditions

作者:Felcenloben Isaura; Zyromska Edyta; Piasecki Tomasz; Rossowska Joanna; Kedzierska Anna; Nowak Marcin; Zyromski Marcin; Chelmonska Soyta Anna
来源:Central European Journal of Immunology, 2017, 42(1): 39-53.
DOI:10.5114/ceji.2017.67317

摘要

Aim o the study: To compare the potential of CD4+CD25 cells, isolated from both healthy rats and rats with CIA (Collagen-Induced Arthritis), for differentiation into regulatory T cells in the presence of all-trans retinoic acid in order to learn more about the activation mechanisms and therapeutic potential of regulatory T cells. Material and methods: Sorted CD4+CD25 cells were cultured in vitro with/without ATRA, and then the frequency of regulatory T cells and their ability to secrete IL-10 by CD4+ FOXP3+ cells was examined. Gene expression of the foxp3,rar alpha,rar beta, rxr beta, and ppar pis and protein expression of the Rar alpha, Rar beta, and Rxr beta in cells after stimulation with ATRA were also investigated. Results: CD4+CD25 cells isolated from healthy animals or from animals with CIA are characterised by different potential of the differentiation into CD4+CD25+ FOXP3+ cells. Retinoic acid receptor Rxr beta is present in the CD4+CD25 cells isolated from rats with CIA. Conclusions: We showed that although ATRA did not increase the frequency of Treg in culture, it significantly increased expression of rar beta and rxr beta only in lymphocytes taken from diseased animals and foxp3 expression only in healthy animals. Moreover, after ATRA stimulation, the frequency of Treg-produced IL-10 tended to be lower in diseased animals than in the healthy group. The results imply that the potential of nadVe cell CD4 lymphocytes to differentiate into Tregs and their putative suppressive function is dependent on the donor's health status.

  • 出版日期2017