Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D

Abstract

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes plays a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of Th17 and Th1, but not Th2 responses in human PBMCs. P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA and IL-17RC, and triggered IL-17 secretion from CD4+, but not CD8+ T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naïve CD4+CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6 and TGF-β neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and vitamin D could be effective tools to modulate Th17-mediated diseases such as acne.

Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation

“…Recent reports suggest that T-helper type 17 (Th17) and Th1 lymphocytes are involved in the pathogenesis of acne (1)(2)(3). Systemic isotretinoin remains the most efficient treatment for acne, but its complete mechanism of action is unknown.…”

Comparison the Antibacterial Activity of Vitamin D2 and D3

“…[26] Inflammation resulting from the immune response targeting Propionibacteriumacnes(P. acnes)has a significant role in acne pathogenesis. In a recent study, it has been demonstrated that P. acnes is a potent inducer ofTh17, and that 1,25OH2D inhibits P. acnes-induced Th17 differentiation, and thereby could be considered as an effective tool in modulating acne ,that demonstrate the important role of vitamin D in skin infections [27] . Results of [28] showed that Gram negative bacteria were more resistant to vitamin E effect than Gram positive bacteria, this resistance towards antibacterial substance may be related to lipopolysaccharides (LPS) in their outer membrane.…”

Perbandingan Kadar Interleukin-17 Serum Pasien Akne Vulgaris Tipe Papulopustular dengan Komedonal

“…Interleukin-17A atau yang sering disebut pula sebagai IL-17 8 merupakan sitokin proinflamasi yang poten, 9 diproduksi oleh sel T helper (Th)17 yaitu merupakan subset dari sel T CD4 + . 8 IL-17, berperan penting dalam pembentukan penyakit inflamasi, 10 yaitu antara lain psoriasis, artritis reumatoid, penyakit Crohn, penyakit obstruksi saluran napas, sklerosis sistemik, 9 penyakit kulit infeksi seperti Staphylococcus, 11 serta penyakit kulit inflamasi seperti dermatitis kontak alergi dan atopik. Pada AV, sekresi IL-17 dari sel Th17 didapatkan melalui diferensiasi sel T CD4 + dengan bantuan ketiga sitokin yang diinduksi oleh P. acnes, yaitu IL-1β, IL-6, dan TGF-β.…”

“…11 Pada serum pasien AV dengan lesi inflamasi didapatkan peningkatan kadar IL-17, TNF-α, IL-4, dan interferon (IFN)-γ dibanding dengan orang normal. 12 Penelitian ini bertujuan membandingkan apakah ada perbedaan kadar IL-17 di dalam serum antara pasien AV tipe papulopustular dan AV tipe komedonal.…”