Oncotarget

Research Papers: Immunology:

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

Karin M. E. Andersson, Mikael Brisslert, Nicola Filluelo Cavallini, Mattias N. D. Svensson, Amanda Welin, Malin C. Erlandsson, Michael J. Ciesielski, Gergely Katona, Maria I. Bokarewa _

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Oncotarget. 2015; 6:20043-20057. https://doi.org/10.18632/oncotarget.4994

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Abstract

Karin M. E. Andersson1,*, Mikael Brisslert1,*, Nicola Filluelo Cavallini1, Mattias N. D. Svensson1,4, Amanda Welin1, Malin C. Erlandsson1, Michael J. Ciesielski2, Gergely Katona3, Maria I. Bokarewa1

1Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

2Department of Neurosurgery, Roswell Park Cancer Institute and State University of New York School of Medicine and Biomedical Sciences, Buffalo, NY, USA

3Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden

4Division of Cellular Biology, La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA

*These authors have contributed equally to this work

Correspondence to:

Maria I. Bokarewa, e-mail: maria.bokarewa@rheuma.gu.se

Keywords: Immune response, Immunity, Immunology and Microbiology Section, survivin, Bcl6, T-cells, autoimmunity, arthritis

Received: May 19, 2015     Accepted: July 30, 2015     Published: August 12, 2015

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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