Figure 7: DC activation through ITAM-Syk-CARD9 signalling is required for the priming of hapten-specific T cells. | Nature Communications

Figure 7: DC activation through ITAM-Syk-CARD9 signalling is required for the priming of hapten-specific T cells.

From: An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells

Figure 7

Haptens, but not irritants, can ‘haptenize’ proteins to form a hapten self-protein complex, which is eventually presented by DCs as an altered-self antigen to trigger TCRs. In addition, haptens but not irritants have the capacity to activate ITAM-Syk signalling in DCs. Syk activation not only induces the CARD9/BCL10-regulated NF-κB activation required for the intracellular synthesis of pro-IL-1α/β (SIGNAL 1), but also induces ROS generation required for NLRP3 inflammasome activation (SIGNAL 2). K+ efflux and P2X7 also contribute to inflammasome activation. As a result, bioactive IL-1α/β are secreted by antigen-presenting DCs, which in turn stimulates naïve T cells through the IL-1R1-Myd88 pathway, delivering essential additional signals required for the priming of hapten-specific T cells in the dLNs. CARD9/BCL10-regulated NF-κB activation is also required for hapten-induced IL-6 and IL-12 production that drives effector T-cell differentiation.

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