FIGURE 1.

Production of IL-10 by ICOS-expressing T cells with regulatory function. CD4⁺ICOS⁺ Tregs express high levels of IL-10 but smaller amounts of TGF-β compared with ICOS^– Tregs. Transcriptome and FACS analyses have demonstrated a correlation between the increased ICOS expression on Tregs with the high expression levels of CD5, CD69, CXCR3, and T-bet as well as some checkpoint inhibitors, such as CTLA-4, TIGIT, Lag3, and PD-1, (15, 56, 57) some of which have been shown to promote the transcription of the IL-10 gene, contributing to high levels of IL-10 secretion together with ICOS. In addition, other ICOS-expressing regulatory cells, such as Tr1, Treg-of-B cells, and Tfr cells, can also be the source of IL-10.