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 has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (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 from CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6, and transforming growth factor-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 D could be effective tools to modulate Th17-mediated diseases such as acne.

• Authors: George W Agak, Min Qin, Jennifer Nobe, Myung-Hwa Kim, Stephan R Krutzik, Grogan R Tristan, David Elashoff, Hermes J Garbán, Jenny Kim
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 134 Issue 2 Pg. 366-373 (Feb 2014) ISSN: 1523-1747 [Electronic] United States
• PMID: 23924903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• IL17A protein, human
• IL17RA protein, human
• IL17RC protein, human
• Interleukin-17
• Interleukins
• Nuclear Receptor Subfamily 1, Group F, Member 1
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RORA protein, human
• RORC protein, human
• Receptors, Interleukin
• Receptors, Interleukin-17
• Vitamin A
• Vitamin D

Topics

• Acne Vulgaris (immunology, microbiology, pathology)
• CD4-Positive T-Lymphocytes (cytology, immunology, microbiology)
• Cell Differentiation (immunology)
• Gram-Positive Bacterial Infections (immunology, pathology)
• Humans
• Interleukin-17 (immunology, metabolism)
• Interleukins (immunology, metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 1 (immunology, metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (immunology, metabolism)
• Propionibacterium acnes (immunology)
• Receptors, Interleukin (immunology, metabolism)
• Receptors, Interleukin-17 (immunology, metabolism)
• Th1 Cells (cytology, immunology, microbiology)
• Th17 Cells (cytology, immunology, microbiology)
• Vitamin A (metabolism)
• Vitamin D (immunology)
• Interleukin-22