TGF-β promotes the conversion of human CD5low cDC2s to tolerogenic CD5high cDC2s

Human blood CD1c+ cDC2s can be divided into two functionally distinct subpopulations according to their CD5 expression. CD5high and CD5low cDC2s differ significantly in their gene expression, cytokine production, antigen presentation, and T cell polarization. However, the plasticity of CD5high and CD5low cDC2s was unknown. We found that about 40% CD5low cDC2s upregulated their CD5 expression when cultured in the presence of TGF-β. Transcriptome analysis revealed that the converted CD5high cDC2s are closer to cultured CD5high cDC2s, separating form unconverted CD5low cDC2s. Converted CD5high cDC2s with higher IRF4 upregulated some steady-state DC mature molecules, such CCR7, CD86, PD-L1 and CCL22. Unconverted CD5low cDC2s with higher MAFB upregulated some monocyte signature genes, such CCR2, CSF1R and CCL2. Moreover, Converted CD5high and unconverted CD5low cDC2s were significantly different in inducing CD4+ T cell polarization. Specifically, converted CD5high cDC2s recruited and induced more Treg cells than unconverted CD5low cDC2s. We also found that the ratio of CD5high cDC2s are significantly higher in colorectal tumor tissue comparing with paired paratumor tissue. In summary, TGF-β can effectively promote the conversion from CD5low cDC2s to CD5high cDC2s accompanied by phenotype and function change. This may be another mechanism which contributes to TGF-β induced immune suppression. mRNA profiles of CD5high and CD5low cDC2s after they are cultured in the presence of TGF-β and then sorted according to CD5 expression level