Fig. 2

Cytokine signaling pathways. JAK-STAT pathway: cytokines activate the JAK/STAT pathway and trigger the secretion of a variety of pro-inflammatory mediators. TLRs pathways: Stimulated by the PAMPs or DAMPs, TLRs promote cytokine storm mainly via two signaling pathways: the canonical TLRs-MyD88-MAPK pathway and the noncanonical TLRs-TRIF-IRF3 pathway. The TLRs could also regulate the transcription of NF-κB and cause cytokine production. TCR/BCR/NF-κB pathway: cytokines bind to receptors on immune cells and induces NF-κB pathway activation and induce the activation of multiple cytokines. NLRP3 pathway: the activation of NLRP3 requires two signals: The first signal was the activation of inflammatory transcription factor NF-κB, thereby upregulating pro-IL-1β, pro-IL-18, NLRP3, and caspase-1. The second signaling process was NLRP3 induces the formation of super-molecule signaling inflammasome complex by recruiting ASC, leading to IL-1β maturation and secretion of IL-18, as well as to gasdermin D-mediated pyroptosis. PANoptosome pathway: PANoptosome inflammasome complex was assembled and activated by immune disturbance, promoting caspase-dependent and MLKL-dependent PANoptotosis. Abbreviations: JAK Janus Kinase, STAT signal transducer and activator of transcription, TLRs Toll-like receptors, DAMPs damage-associated molecular patterns, PAMPs pathogen-associated molecular patterns, TRIF TIR domain-containing adapter inducing IFN-β, TRAF tumor necrosis factor receptor-associated factor, IRF3 interferon regulatory factor 3, MyD88 myeloid differentiation primary response 88, MAPK mitogen-activated protein kinase, AP-1 activating protein-1, TCR T-cell receptor, BCR B-cell receptor, NF-κB Nuclear Factor kappa B, IκB inhibitor of NF-κB, NLRP3 the NLR family pyrin domain containing 3, NEK7 NIMA-related kinase 7, ASC apoptosis related spot like protein, GSDMD gasdermin D, ZBP1 Z-DNA binding protein 1, AMI2 absent in melanoma 2, MLKL mixed-lineage kinase domain-like pseudokinase. The figure was created with the assistance of FIGDRAW