TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells.
Human Th17 clones and circulating Th17 cells showed lower susceptibility to the anti-proliferative effect of TGF-beta than Th1 and Th2 clones or circulating Th1-oriented T cells, respectively. Accordingly, human Th17 cells exhibited lower expression of clusterin, and higher Bcl-2 expression and reduced apoptosis in the presence of TGF-beta, in comparison with Th1 cells. Umbilical cord blood naïve CD161(+)CD4(+) T cells, which contain the precursors of human Th17 cells, differentiated into IL-17A-producing cells only in response to IL-1beta plus IL-23, even in serum-free cultures. TGF-beta had no effect on constitutive RORgamma t expression by umbilical cord blood CD161(+) T cells but it increased the relative proportions of CD161(+) T cells differentiating into Th17 cells in response to IL-1beta plus IL-23, whereas under the same conditions it inhibited both T-bet expression and Th1 development. These data suggest that TGF-beta is not critical for the differentiation of human Th17 cells, but indirectly favors their expansion because Th17 cells are poorly susceptible to its suppressive effects.
Santarlasci
Veronica
V
Centre of Excellence DENOthe, University of Florence, Florence, Italy.
Maggi
Laura
L
Capone
Manuela
M
Frosali
Francesca
F
Querci
Valentina
V
De Palma
Raffaele
R
Liotta
Francesco
F
Cosmi
Lorenzo
L
Maggi
Enrico
E
Romagnani
Sergio
S
Annunziato
Francesco
F
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D051152:Clusterin / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D053583:Interleukin-1beta / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology
C495242:CLU protein, human; D051152:Clusterin; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta