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

体外条件下从胶原诱导性关节炎大鼠和健康大鼠中分离的幼稚 CD4+CD25- 细胞的分化全反式维甲酸反应

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作者:Isaura Felcenloben, Edyta Żyromska, Tomasz Piasecki, Joanna Rossowska, Anna Kędzierska, Marcin Nowak, Marcin Żyromski, Anna Chełmońska-Soyta

Conclusions

We showed that although ATRA did not increase the frequency of Treg in culture, it significantly increased expression of rarβ and rxrβ 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 naïve cell CD4 lymphocytes to differentiate into Tregs and their putative suppressive function is dependent on the donor's health status.

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, rarα, rarβ, rxrβ, and ppar β/δ and protein expression of the Rarα, Rarβ, and Rxrβ in cells after stimulation with ATRA were also investigated.

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, rarα, rarβ, rxrβ, and ppar β/δ and protein expression of the Rarα, Rarβ, and Rxrβ 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 Rxrβ 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 rarβ and rxrβ 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 naïve cell CD4 lymphocytes to differentiate into Tregs and their putative suppressive function is dependent on the donor's health status.

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