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. 2020 Nov 27;90:107225. doi: 10.1016/j.intimp.2020.107225

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Fig. 5 — IL-6 cell signalling can occur three ways: (A) Classic pathway (or cis pathway) involves membrane bound IL-6R and gp-130 whereas; (B) Trans pathway involves IL-6 binding with soluble (sIL-6R) along with gp-130. Both classic and trans pathway mediate JAK/STAT signalling to mediate CRS (C) Trans presentation occurs via dendritic cells (DC) which trans-present IL-6 via their own IL-6R to cognately interact with T cells (termed IL-6 ‘cluster signalling’), resulting in their differentiation to Th17 cells via JAK-STAT signalling. The JAK/STAT signalling (by both cis and trans signalling) and RAS-RAF, SRC-YAP-NOTCH and AKT-P13K promote the transcription of multiple downstream genes associated with T-cell clonal amplification, B-cell differentiation, acute phase response production.