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. 2021 Nov 4;12:761946. doi: 10.3389/fimmu.2021.761946

Figure 2.

Figure 2

The role of PAD2 in METosis and pyroptosis in macrophages. Pathogens trigger calcium influx into cytoplasm of macrophages. Subsequently, PAD2 is activated due to elevated levels of calcium. Activated PAD2 translocates into the nucleus to induce histone citrullination and chromatin decondensation, leading to METosis. Also, PAD2 mediates pyroptosis via citrullinating ASC. Citrullinated ASC participates in the assembly of inflammasomes which activate Caspase-1. Caspase-1 facilitates the maturation of IL-1β and IL-18 via cleaving their precursors. Meanwhile, Caspase-1 cleaves and activates PFMs which insert into plasma membrane to create pores allowing massive water to flux in. As a result, macrophages swell and rupture to accomplish pyroptosis, releasing mature IL-1β and IL-18. ASC: apoptosis-associated speck-like protein containing a CARD domain; IL, interleukin; METosis, macrophage death with release of macrophage extracellular traps; PAD2, type 2 peptidylarginine deiminase; PFMs, pore forming molecules; PRR, pattern recognition receptor.