Effect of p53 activation through targeting MDM2/MDM4 heterodimer on T regulatory and effector cells in the peripheral blood of Type 1 diabetes patients

被引：9

作者：

Pellegrino, Marsha ^{[1
]}

Traversi, Gianandrea ^{[1
]}

Arena, Andrea ^{[1
]}

Cappa, Marco ^{[2
]}

Rosado, M. Manuela ^{[3
]}

Andreani, Marco ^{[4
]}

Delfino, Domenico, V ^{[5
]}

Moretti, Fabiola ^{[6
]}

Fierabracci, Alessandra ^{[1
]}

机构：

[1] Bambino Gesu Pediat Hosp, Infectivol & Clin Trials Res Dept, IRCCS, Rome, Italy

[2] Bambino Gesu Pediat Hosp, Endocrinol Dept, IRCCS, Rome, Italy

[3] Bambino Gesu Pediat Hosp, IRCCS, Res Labs, Rome, Italy

[4] Bambino Gesu Pediat Hosp, IRCCS, Transplantat Immunogenet Lab, Rome, Italy

[5] Univ Perugia, Dept Med, Sect Pharmacol, Perugia, Italy

[6] Natl Res Council Italy CNR, Inst Cell Biol & Neurobiol, Rome, Italy

来源：

PLOS ONE | 2020年 / 15卷 / 01期

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; TUMOR-SUPPRESSOR GENE; AUTOIMMUNE-DISEASES; ARTHRITIS; POLYMORPHISM; EXPRESSION; ANTIBODIES; MUTATIONS; TP53; MDM2;

D O I：

10.1371/journal.pone.0228296

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Various immunotherapies for the treatment of type 1 diabetes are currently under investigation. Some of these aim to rescue the remaining beta cells from autoimmune attack caused by the disease. Among the strategies employed, p53 has been envisaged as a possible target for immunomodulation. We studied the possible effect of p53 activation on Treg subsets and Treg/Teff balance in type 1 diabetes patients' PBMC. Upon p53 activation, we observed an increase in CD8+ Treg and activated CD8+ Teff whilst CD8+ Teff cells significantly decreased in healthy PBMC when stimulated with anti-CD3/CD28. No effect was detected on percentages of CD4+ Treg, while a reduction was seen in CD4+ Teff cells and an increase in activated CD4+ Teff cells. In patients' PBMC, upon p53 activation followed by 6 days of anti-CD3/CD28 stimulation, CD8+ Treg and activated CD8+ Teff were increased while CD8+ Teff were decreased. No differences were detected in the CD4+ counterparts. CD8+ Teff PD1+, CD8+ Teff PD1low were increased upon p53 activation in type 1 diabetics compared to controls while CD8+ Teff PD1high were increased in both groups. The same increased percentages were detected for CD4+ counterparts. CD4+ Treg PD1high cells were decreased in diabetics upon p53 activation at day 6 of anti-CD3/CD28 stimulation. In conclusion, a Teff dysregulation is observed upon p53 activation suggesting that molecules promoting p53 cannot be used for therapy in type 1 diabetics.

引用

页数：20

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