Survivin co-ordinates formation of follicular T-cells acting in synergy with Bcl-6.
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.
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Karin M E
KM
Andersson
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Mikael
M
Brisslert
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Nicola Filluelo
NF
Cavallini
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.|Division of Cellular Biology, La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA.
Mattias N D
MN
Svensson
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Amanda
A
Welin
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Malin C
MC
Erlandsson
Department of Neurosurgery, Roswell Park Cancer Institute and State University of New York School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
Michael J
MJ
Ciesielski
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Gergely
G
Katona
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Maria I
MI
Bokarewa
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017433:Protein Structure, Secondary; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D000077022:Survivin
C084103:BCL6 protein, human; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D000077022:Survivin; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1
Bcl6; Immune response; Immunity; Immunology and Microbiology Section; T-cells; arthritis; autoimmunity; survivin