Survivin co-ordinates formation of follicular T-cells acting in synergy with Bcl-6

Oncotarget
Karin M E AnderssonMaria I Bokarewa

Abstract

Follicular T helper (Tfh) cells are recognized by the expression of CXCR5 and the transcriptional regulator Bcl-6. Tfh cells control B cell maturation and antibody production, and if deregulated, may lead to autoimmunity. Here, we study the role of the proto-oncogene survivin in the formation of Tfh cells. We show that blood Tfh cells of patients with the autoimmune condition rheumatoid arthritis, have intracellular expression of survivin. Survivin was co-localized with Bcl-6 in the nuclei of CXCR5+CD4 lymphocytes and was immunoprecipitated with the Bcl-6 responsive element of the target genes. Inhibition of survivin in arthritic mice led to the reduction of CXCR5+ Tfh cells and to low production of autoantibodies. Exposure to survivin activated STAT3 and induced enrichment of PD-1+Bcl-6+ subset within Tfh cells. Collectively, our study demonstrates that survivin belongs to the Tfh cell phenotype and ensures their optimal function by regulating transcriptional activity of Bcl-6.

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Citations

Dec 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mattias N D SvenssonMaria I Bokarewa
May 8, 2019·Journal of Cellular Physiology·Parisa ZafariMahdi Taghadosi
Mar 6, 2019·International Journal of Rheumatic Diseases·Hamidreza EbrahimiyanMahdi Mahmoudi

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Methods Mentioned

BETA
flow cytometry
ChIP
PCR
immunoprecipitation
ELISA
FACS
Protein Assay

Software Mentioned

Quantity One
CAPRI
GraphPad Prism
Cluspro2
FACSDiva
GraphPad
IDEAS
FlowJo

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