Figure 1.

Proposed involvement of SerpinB1 and SLPI in NET formation and immunogenic function. (1) In resting neutrophils, NE localizes to primary granules, whereas SerpinB1 and SLPI localize to the cytoplasm and/or secondary granules. (2) In activated neutrophils that infiltrate psoriatic skin, NE translocates to the nucleus, where it contributes to chromatin decondensation. SLPI and SerpinB1 translocate independently to the nucleus, where they regulate NET formation at the level of chromatin decondensation. Once in the nucleus, SLPI restricts the NE-mediated cleavage of histones, whereas SerpinB1 limits chromatin decondensation through other, yet-to-be-identified mechanisms. (3) The inhibition of NET formation is partial, and the decondensed chromatin containing NE, as well as SerpinB1 and SLPI, is deposited into the extracellular milieu. (4) SLPI produced by keratinocytes in lesional psoriatic skin is sequestered on NETs. (5) SLPI-competent NETs stimulate the pro-inflammatory and/or skin healing function that results from skin damage through the production of IFNI by pDCs.