Why is Some Skin Prone to Inflammation, or Not? New Research Points to ZNF750.

The authors conclude, 'Our findings explain how the skin’s surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs.'
The authors conclude, "Our findings explain how the skin’s surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs."
Pormezz at Adobe Stock

If the skin constantly experiences inflammatory stimuli, why isn't everyone's skin constantly inflamed? New research points to some answers.

It turns out that the protein ZNF750, AKA zinc finger protein 750, doesn't just protect the skin's barrier; it also silences skin inflammation, per a new study by researchers at University of California San Diego School of Medicine published in the journal Immunity.

Per the study, ZNF750, which is "expressed only in differentiated keratinocytes," leverages the histone demethylase KDM1A/LSD1 to silence genes coding for inflammatory pattern recognition receptors (PRR; TLR3, IFIH1/MDA5 and DDX58/RIG1), which "detect damage or pathogens" and are found in undifferentiated keratinocytes in the epidermis. 

PRR-instigated inflammation is associated with psoriasis and seborrheic dermatitis.

Therefore, those who experience a loss of ZNF750 or KDM1A in human keratinocytes may be prone to chronic inflammation.

This mechanism perhaps explains why, while inflammatory stimulus regularly interacts with the skin, inflammation is more present in certain individuals. 

Notably, as keratinocytes become differentiated, they move toward the skin's surface and, simultaneously, express much less PRR. This process diminishes immune responses, the researchers argue.

The authors conclude, "Our findings explain how the skin’s surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs."


More in Literature/Data