Fig. 8: Proposed model of the molecular pathways whereby mMIC and sMIC differentially regulate NK cell function. | Communications Biology

Fig. 8: Proposed model of the molecular pathways whereby mMIC and sMIC differentially regulate NK cell function.

From: Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation

Fig. 8

Engagement of the receptor NKG2D to the two forms of MIC ligand, mMIC, and sMIC leads to distinct signaling cascades resulting in activation of NK cell cytotoxicity and inflammatory cytokine/chemokine production, respectively. mMIC-NKG2D interaction delivers a regulated stimulation through canonical immune synapse formation and selectively activates PLCγ2/SLP-76/Vav-1 and ERK/JNK signaling axis for NK cell cytotoxicity and upregulation of T-bet for IFNγ secretion. Conversely, the lack of canonical immune synapse formation upon sMIC-NKG2D interaction delivers a chronic and deregulated stimulation that results in activation of CBM-signalosome-mediated pro-inflammatory pathways. The activation of CBM-signalosome pathways is associated with persistent activation of Fyn/ADAP and PKC-θ pathways. The ITAM immediate downstream molecule Lck is required for both mMIC- and sMIC-stimulated events.

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