Rhil 22

ALCL cell lines were obtained from DSMZ, Braunschweig, Germany. For cytokine complementation experiments, recombinant human Interleukin-10 (10 ng/ml, rh IL-10, Immunotools, Friesoythe, Germany) or rhIL-22 (20 ng/ml, Immunotools) were used. For detection of downstream targets, ALCL cells were incubated with TYK2 inhibitors or pan-JAK inhibitors (including 1 µM JAK inhibitor I, Calbiochem, San Diego, CA, USA) for 3 or 6 h and then incubated with IFN-α for 10 min before immunoblot analysis. Description of quantitative RT-PCR, flow cytometry, cytokine arrays and immunohistochemistry, shRNA sources, CRISPR/Cas9 genome editing and murine lymphoma models can be found in Supplementary Methods.

The MTT assay 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide was performed on HK2 cells and K4 cells to evaluate the metabolic activity induced by IL‐22. Cells were seeded at 5000 cells/well in a 96‐well microculture plate. After cell adhesion for 4 h, various concentrations of recombinant human IL‐22 (rhIL‐22) (Immunotools, Friesoythe, Germany) 1 ng/mL, 10 ng/mL and 50 ng/mL in serum‐free media were added to the wells followed by continuous incubation for 48 h. Cells treated with serum‐free medium only or 10% FBS supplemented media served as negative and positive controls, respectively. Then, 15 μL MTT (5 mg/mL) (Promega, Wisconsin, USA) was added to each well and the plate was incubated at 37°C for another 3 h, after which 100 μL 10% HCl‐SDS was added to each well. The plate was kept at room temperature overnight. Optical density (OD) was quantified via a 96‐well plate reader to record the absorbance at 570 nm. OD is shown after normalization to negative controls.