Journal
ONCOTARGET
Volume 6, Issue 24, Pages 20043-20057Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4994
Keywords
Immunology Section; survivin; Bcl6; T-cells; autoimmunity; arthritis
Categories
Funding
- Swedish Research Council [521-2014-2637]
- Medical Society of Goteborg
- Swedish Association against Rheumatism
- King Gustaf V:s 80-year Foundation
- Commission of European Union [FP7-Health 261460]
- Professor Nanna Swartz Foundation
- Torsten Soderberg's Foundation
- Swedish Foundation for Strategic Research
- Ingabritt and Arne Lundberg's Foundation
- pharmacist Hedberg's Foundation
- University of Goteborg [LUA/ALF431141]
- Western Gotaland county council [LUA/ALF431141]
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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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