GPR15 is not critically involved in the regulation of murine psoriasiform dermatitis.

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.

Offering preconceptional cystic fibrosis carrier couple screening in the absence of established preconceptional care services.

OBJECTIVE: To investigate the feasibility and acceptability of different modes of offering preconceptional carrier screening for cystic fibrosis (CF) in the absence of established preconceptional care services. METHODS: Individuals aged 20-35 years were invited by mail, either by the Municipal Health Services (MHS) or by their own general practitioner (GP) to participate in a screening program with their partner. Pretest education was provided either during a group educational session or during a GP consultation. The reasons given by participants and nonrespondents for (not) responding to the invitation for screening, sociodemographic characteristics, and their attitudes were assessed by means of questionnaires. RESULTS: Of 38,114 individuals who received a first invitation, approximately 20% had a partner with whom they were planning to have children. The response rate, as measured by attendance at either a group educational session or a GP consultation, was not affected by whether the letter was sent by the MHS or the person's GP. However, the response rate was about 2.5 times higher when the letter invited people to make an appointment with their GP for a consultation regarding CF carrier screening than when it invited them to attend an educational group session. A total of 559 couples (96%) consented to have the test after education. Repetition of the invitation increased the response. The main reason given by couples for not responding was "lack of time to attend" or "forgot about it" (48%). Another reason given was that they did not want to know their test results (28%). Eighty-nine percent of participants and 69% of nonrespondents believed that screening should be offered routinely to couples planning to have children. The GPs consulted (n = 18) reported no negative experiences, but due to the extra workload, 11 of them would not consider it to be part of their task. CONCLUSIONS: Among couples planning to have children, there is generally a positive attitude towards routinely offering population-based CF carrier screening. Preconceptional CF carrier screening appeared feasible, both in terms of practical achievements and target group accessibility. Participation varied according to the pretest education setting, with the primary care setting producing the highest rate of attendance.