Fig. 9

CRA activated STAT3 signaling by interacting with IL-6R. Panel A. IL-6R expression in CRC cancer cell lines. Gene expression of IL-6R in 57 CRC cancer cells obtained from the database of The Human Protein Atlas (https://www.proteinatlas.org/). Ninety-four CRC cell lines were shown their IL-6R expression below 10 nTPM. Panel B. IL-6R expression in T cells. Three datasets, including HPA, Monaco, and Schmiedel datasets showed high expression of IL-6R in different T cell subsets. Panel C. Docking of CRG into the D3 domain of IL-6Rα (PBD code: 1N26). The amino acids, including Thr218, Asp221, Trp225, Ser228, Arg231, and His256 that potentially interacted with CRG were highlighted. Panel D. Neutralizing IL-6R antibodies declined CRA-induced STAT3 activation and IL-21 production. Splenic T cells were pre-treated with 1 μg/mL anti-IL-6R antibodies for 30 min and then treated with 6 μg/mL CRA for 24 h. The STAT3 and IL-21 expression were analyzed by qPCR