title: CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation.
abstract: IL-17-producing CD4(+) T helper (Th17) cells are important for immunity against extracellular pathogens and in autoimmune diseases. The factors that drive Th17 development in human remain a matter of debate. Here we show that, compared with classic CD28 costimulation, alternative costimulation via the CD5 or CD6 lymphocyte receptors forms a superior pathway for human Th17-priming. In the presence of the Th17-promoting cytokines IL-1β, IL-6, IL-23, and transforming growth factor-β (TGF-β), CD5 costimulation induces more Th17 cells that produce higher amounts of IL-17, which is preceded by prolonged activation of signal transducer and activator of transcription 3 (STAT3), a key regulator in Th17 differentiation, and enhanced levels of the IL-17-associated transcription factor retinoid-related orphan receptor-γt (ROR-γt). Strikingly, these Th17-promoting signals critically depend on CD5-induced elevation of IL-23 receptor (IL-23R) expression. The present data favor the novel concept that alternative costimulation via CD5, rather than classic costimulation via CD28, primes naive T cells for stable Th17 development through promoting the expression of IL-23R.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: de Wit
authors.forename: Yuri
authors.initials: Y
authors.lastname: Souwer
authors.forename: Astrid J
authors.initials: AJ
authors.lastname: van Beelen
authors.forename: Rosa
authors.initials: R
authors.lastname: de Groot
authors.forename: Femke J M
authors.initials: FJ
authors.lastname: Muller
authors.forename: Hanny
authors.initials: H
authors.lastname: Klaasse Bos
authors.forename: Tineke
authors.initials: T
authors.lastname: Jorritsma
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D018956:CD5 Antigens; C515500:IL23R protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human