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. 2021 Jun 1;12:683401. doi: 10.3389/fimmu.2021.683401

Figure 2.

Figure 2

Distinct coexpressed groups of cytokines overproduced in MPNs. Data specific to MF, also utilized in Fisher et al. (48). (A, B) Presence or absence of tandem regulation of cytokine induction by TPO. Biaxial plots show in rows (from top to bottom) ex vivo cell samples from healthy control blood and blood from the JAK2 V617F mutant MF patient MF20. Columns show cytokines as identified in cells by mass cytometry (CyTOF) after 4-hour incubation either without stimulation (Basal) or stimulated by TPO. (A) In monocytes, TNF (Y axis) showed coexpression with IL-8/CXCL8 (X axis) when induced by TPO. Combined induction is illustrated by schematic below lower right plot. (B) TGFβ (X axis) showed minimal basal coexpression with TNF (Y axis) in monocytes. TPO stimulation, however, induced TNF but not TGFβ, as illustrated by schematic under lower right plot. (C) Schematic depicting “axis” groups of cytokines overproduced in MF myeloid cells ex vivo. The majority of cytokines could be separated into TNF or TGFβ “axis” groups (related to biaxial plots in A, B), based on co-expression with either TNF or TGFβ after stimulation with TPO, TNF, or a TLR receptor ligand (R848 or PAM3CSK4), with Pearson R>0.25 (48). Of 15 cytokines assayed by CyTOF in Fisher et al. (48), only VEGF and IFNγ failed to demonstrate coexpression with either TNF or TGFβ, while IL-8/CXCL8 showed some evidence of coregulation with both (R>0.25).