TGF-β and IL-21 cooperatively stimulate activated CD8+ T cells to differentiate into Tc17 cells

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8+T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

“…5D ). Although IL-21 has been well known as an important cytokine for IL-17 + CD8 + cell differentiation ( 51 61 ), our data underscore the importance of IL-1β for the production of IL-17 in CD8 + T cells via IL-21-mediated IL-1RI expression. Considering that IL-21 is expressed by CD4 + T cells early during influenza infection ( 62 ), our finding may give another explanation on Tc17-mediated protection of influenza or other viral infections by enhanced CTL function via IL-21-IL-1RI-IL-1β axis.…”

MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells

“…TGF-β1 signaling is not required to maintain oral Tc17 cells in LC ΔMHC-II mice TGF-β1 is essential in vitro to differentiate naïve CD8 T cells towards a Tc17 phenotype (17,45). To investigate the in vivo requirement for TGF-β1 in Tc17 differentiation and/or maintenance, we disrupted TGF-β-dependent signaling in LC ΔMHC-II mice with the kinase inhibitor LY364947 (26).…”

Friend or Foe – Tc17 cell generation and current evidence for their importance in human disease

“…TGF-β is a common component of cytokine cocktails for the in vitro generation of Tc17 cells, but it has been shown to be dispensable for Tc17 cell generation in vivo : Transgenic animals carrying a dominant negative form of the TGF-β receptor II are still able to generate IL-17 + CD8 + T cells (but fail to generate IL-17 + CD4 + T cells), and neutralization of TGF-β only has little effect on Tc17 frequencies, highlighting different requirements for CD8 + and CD4 + IL-17 + T cell differentiation [ 140 , 141 ]. The cellular requirement for IL-6 signaling to induce a Tc17 program depends on the cell’s activation status: While IL-6 is frequently used in in vitro differentiation cocktails for the generation of Tc17 cells from naïve CD8 + T cells, it might not be relevant for the conversion of already differentiated murine Tc1 cells into Tc17 cells [ 142 ]. This is likely due to the expression pattern of the IL-6 receptor, which is expressed on naïve, but not on activated CD8 + T cells [ 142 ].…”

“…The cellular requirement for IL-6 signaling to induce a Tc17 program depends on the cell’s activation status: While IL-6 is frequently used in in vitro differentiation cocktails for the generation of Tc17 cells from naïve CD8 + T cells, it might not be relevant for the conversion of already differentiated murine Tc1 cells into Tc17 cells [ 142 ]. This is likely due to the expression pattern of the IL-6 receptor, which is expressed on naïve, but not on activated CD8 + T cells [ 142 ]. Intracellular effects of IL-6, analyzed in murine CD4 + T cell differentiation, include a RORγt-independent upregulation of the Il21 gene, and RORγt-dependent effects such as the expression of Il17 [ 124 ].…”