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. Author manuscript; available in PMC: 2021 Nov 21.
Published in final edited form as: Sci Immunol. 2021 May 21;6(59):eabe1935. doi: 10.1126/sciimmunol.abe1935

Figure 7. Model for how HDAC8 and 9 maintain immune tolerance in the skin.

Figure 7.

HDAC8 and HDAC9 are expressed in keratinocytes and decrease cytokine expression in response to commonly encountered inflammatory stimuli. When these HDACs are inhibited, keratinocytes mount a greater inflammatory response to stimulation by TLR ligands. This response includes release of IFN-β that enables a DC maturation and subsequent T cell proliferation. HDAC8 and HDAC9 act to decrease acetylation of the MAP2K3 gene. Inhibition of HDAC8 and HDAC9 leads to increased acetylation, activation of the FACT complex and subsequent enhanced transcription of MAP2K3. This primes keratinocytes to increase cytokine expression in response to TLR stimuli.