TY - JOUR
T1 - CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation
AU - de Wit, Jelle
AU - Souwer, Yuri
AU - van Beelen, Astrid J.
AU - de Groot, Rosa
AU - Muller, Femke J. M.
AU - Klaasse Bos, Hanny
AU - Jorritsma, Tineke
AU - Kapsenberg, Martien L.
AU - de Jong, Esther C.
AU - van Ham, S. Marieke
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - https://doi.org/10.1182/blood-2011-05-352682
DO - https://doi.org/10.1182/blood-2011-05-352682
M3 - Article
C2 - 21926348
SN - 0006-4971
VL - 118
SP - 6107
EP - 6114
JO - Blood
JF - Blood
IS - 23
ER -