| First Author | Sezin T | Year | 2019 |
| Journal | J Dermatol Sci | Volume | 94 |
| Issue | 1 | Pages | 196-204 |
| PubMed ID | 30935778 | Mgi Jnum | J:290709 |
| Mgi Id | MGI:6443353 | Doi | 10.1016/j.jdermsci.2019.01.008 |
| Citation | Sezin T, et al. (2019) GPR15 is not critically involved in the regulation of murine psoriasiform dermatitis. J Dermatol Sci 94(1):196-204 |
| abstractText | BACKGROUND: GPR15 has been implicated in the pathogenesis of T cell-driven inflammation of the skin and the gut. Expression levels of the GPR15 ligand GPR15 L are increased in psoriatic skin and considered as potential biomarker for the treatment response to anti-IL-17 antibody therapies. However, the significance of the GPR15 L/GPR15 for the pathogenesis of psoriasis and the mechanisms regulating GPR15 L expression are still elusive. OBJECTIVE: To determine the significance of GPR15 signaling in mouse models of psoriasis. METHODS: We addressed the role of the GPR15 L/GPR15 in the Aldara-induced psoriasiform dermatitis (AIPD) and the IL-23-induced dermatitis model. In both models, we charted the expression levels of GPR15 L in the skin and assessed the significance of GPR15 L/GPR15 by examining Gpr15(-/-) mice. RESULTS: GPR15 L levels were increased in the AIPD, but not in the IL-23-induced dermatitis model. Deficiency in Gpr15 did not alter the course of disease neither in the AIPD, nor in the IL-23-induced dermatitis model. In neither model, deficiency in Gpr15 modulated disease on the histopathological or the molecular level. Despite the induction of GPR15 L in the AIPD model, GPR15(+) cells did not accumulate in the skin. CONCLUSION: GPR15 L expression is induced in psoriasiform dermatitis, but the activation of the IL-23/IL-17 axis alone is not sufficient for its induction. This restricts the potential use of GPR15 L levels as biomarker for the treatment response to anti-IL-17 antibody therapy. Our results leave a significant role of GPR15 in the pathogenesis of psoriasiform dermatitis rather unlikely. Hence, GPR15 L probably modulates psoriasiform dermatitis via GPR15-independent pathways. |
