TY - JOUR
T1 - IKZF3/AIOLOs is associated with but not +sufficient T cells for the expression of IL-10 by CD4
AU - Ridley, Michael L.
AU - Fleskens, Veerle
AU - Roberts, Ceri A.
AU - Lalnunhlimi, Sylvine
AU - Alnesf, Aldana
AU - O’Byrne, Aoife M.
AU - Steel, Kathryn J. A.
AU - Povoleri, Giovanni A. M.
AU - Sumner, Jonathan
AU - Lavender, Paul
AU - Taams, Leonie S.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - The expression of anti-inflammatory IL-10 by CD4+ T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-a blockade during T cell stimulation in CD4+ T cell/monocyte cocultures resulted in maintenance of IL-10–producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4+ T cell–only culture system. IL-10+ CD4+ T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10–CD4+ T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb–mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. However, overexpression of IKZF3 was unable to upregulate IL-10 at the mRNA or protein level in CD4+ T cells and did not drive the transcription of the IL10 promoter or putative local enhancer constructs. Collectively, these data indicate that IKZF3 is associated with but not sufficient for IL-10 expression in CD4+ T cells.
AB - The expression of anti-inflammatory IL-10 by CD4+ T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-a blockade during T cell stimulation in CD4+ T cell/monocyte cocultures resulted in maintenance of IL-10–producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4+ T cell–only culture system. IL-10+ CD4+ T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10–CD4+ T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb–mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. However, overexpression of IKZF3 was unable to upregulate IL-10 at the mRNA or protein level in CD4+ T cells and did not drive the transcription of the IL10 promoter or putative local enhancer constructs. Collectively, these data indicate that IKZF3 is associated with but not sufficient for IL-10 expression in CD4+ T cells.
UR - http://www.scopus.com/inward/record.url?scp=85084888925&partnerID=8YFLogxK
U2 - https://doi.org/10.4049/jimmunol.1901283
DO - https://doi.org/10.4049/jimmunol.1901283
M3 - Article
C2 - 32321757
SN - 0022-1767
VL - 204
SP - 2940
EP - 2948
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
IS - 11
ER -