Single-cell RNA sequencing reveals ulcerative colitis patients’ response to anti-TNF-α therapy

We performed single-cell sequencing of intestinal mucosal tissue from eight UC patients at pre- and post- anti-TNF-α therapy prescription and analyzed them with relation to therapy response (response and no-response). We found that responders have different immune cell profiles from non-responders between pre- and post- anti-TNF-α therapy. Specifically, the proportion of cDC3 decreased in all responders after receiving anti-TNF-α therapy, whereas non-responders could not be distinguished from UC patients who had not received anti-TNF-α therapy. When further compared the difference of type 3 conventional dendritic cells (cDC3) from pre- and post-therapy of anti-TNF-α, distinct transcriptomes were identified in responders, while no significantly different genes were found in cDC3 from non-responders. The interactions analysis of ligands and receptors showed that the interactions between HLA-DPA1/DPB1 in fibroblast and TNFSF9 in cDC3, CD44 in fibroblast and TYROBP in cDC3 were significantly weakened in Post-R group compared with Pre-R group. Cell trajectory analysis demonstrated that the cells differentiated to cDC3 significantly decreased in the Post-R group, and the genes related MAPK signaling pathway obviously increased in these cells.