Induction of Regulatory T Cells and Correction of Cytokine Disbalance by Short-Chain Fatty Acids: Implications for Psoriasis Therapy

Commensal microbes modulate the immune system in the colon through short-chain fatty acids, which induce regulatory T cells (Treg). Accordingly, the short-chain fatty acid sodium butyrate (SB) suppressed allergic contact dermatitis in mice through the activation of Treg. There is evidence that Treg exert the capacity to control inflammation in psoriasis. Thus, we were interested in studying the effect of SB in psoriasis, utilizing the imiquimod-induced psoriasis-like skin inflammation model. Topical application of imiquimod induced thickening of the skin, scales, and inflammation. This was associated with an upregulation of IL-17 and down-regulation of IL-10 and FOXP3. Topically applied SB reduced imiquimod-induced inflammation and downregulated IL-17 and induced IL-10 and FOXP3 transcripts. The mitigating effect of SB was due to Treg because it was lost upon depletion of Treg in the depletion of regulatory T cell mice. Treg isolated from the blood of patients with psoriasis were reduced in their suppressive activity, which was normalized by SB. The fewer Treg numbers in the biopsies of psoriatic lesions as well as enhanced IL-17- and IL-6-expression levels and reduced IL-10- and FOXP3-expression levels were restored by SB. These data indicate that psoriasis is associated with an impairment of Treg and an altered cytokine milieu. Short-chain fatty acids appear to restore these alterations, thereby harboring a therapeutic potential for psoriasis.

Automated summary

Commensal microbes modulate the immune system in the colon through short-chain fatty acids, inducing regulatory T cells (Treg) that suppress skin inflammation. Studies have shown that psoriasis patients have reduced suppressive activity of Treg, which can be normalized by short-chain fatty acids. This suggests that short-chain fatty acids have therapeutic potential for psoriasis by restoring Treg function and cytokine levels.