Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D.
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.
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
George W
GW
Agak
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Min
M
Qin
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jennifer
J
Nobe
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Dermatology, College of Medicine, Dankook University, Seoul, South Korea.
Myung-Hwa
MH
Kim
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Stephan R
SR
Krutzik
Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Grogan R
GR
Tristan
Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
David
D
Elashoff
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hermes J
HJ
Garbán
Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Dermatology, Greater Los Angeles Healthcare System Veterans Affairs, Los Angeles, California, USA. Electronic address: JeKim@mednet.ucla.edu.
Jenny
J
Kim
D000152:Acne Vulgaris / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000276:immunology / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology / Q000378:metabolism; D011425:Propionibacterium acnes / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D014801:Vitamin A / Q000378:metabolism*; D014807:Vitamin D / Q000276:immunology*; D000097043:Interleukin-22
D020381:Interleukin-17; D007378:Interleukins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D014801:Vitamin A; D014807:Vitamin D; D000097043:Interleukin-22; C508717:IL17A protein, human; C109985:IL17RA protein, human; C448419:IL17RC protein, human; C539738:RORA protein, human; C539900:RORC protein, human