A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia
We describe the purification from porcine colonic tissue extracts of an agonistic ligand for GPR15 and its functional characterization. In humans, this ligand, which we named GPR15L, is encoded by the gene C10ORF99 and has some features similar to the CC family of chemokines. GPR15L was found in some human and mouse epithelia exposed to the environment, such as the colon and skin. In humans, GPR15L was also abundant in the cervix. In skin, GPR15L was readily detected after immunologic challenge and in human disease, for example, in psoriatic lesions. Allotransplantation of skin from Gpr15l-deficient mice onto wild-type mice resulted in substantial graft protection, suggesting nonredundant roles for GPR15 and GPR15L in the generation of effector T cell responses. Together, these data identify a receptor-ligand pair that is required for immune homeostasis at epithelia and whose modulation may represent an alternative approach to treating conditions affecting the skin such as psoriasis.
We describe the purification from porcine colonic tissue extracts of an agonistic ligand for GPR15 and its functional characterization. In humans, this ligand, which we named GPR15L, is encoded by the gene C10ORF99 and has some features similar to the CC family of chemokines. GPR15L was found in some human and mouse epithelia exposed to the environment, such as the colon and skin. In humans, GPR15L was also abundant in the cervix. In skin, GPR15L was readily detected after immunologic challenge and in human disease, for example, in psoriatic lesions. Allotransplantation of skin from Gpr15l-deficient mice onto wild-type mic...
Psoriasis is thought to be predominantly driven by both CD4+ and CD8+ of the Th17/Tc17 lineages, with an established key role for the Th17 cytokine network, including IL-17 and IL-22. Here, we have explored the possibility that a dysregulation of group 3 innate lymphoid cells (ILC3s) may also be involved in psoriasis pathobiology, by using a modification of our well-established human skin xenotransplant mouse model. Autologous peripheral blood human ILC3s were purified from PBMCs and intradermally injected into normal human skin grafts of healthy donors.
Conclusions PDE4 inhibition reduces inflammatory cell activity and the release of profibrotic cytokines from M2 macrophages, leading to decreased fibroblast activation and collagen release. Importantly, apremilast is already approved for the treatment of psoriasis and psoriatic arthritis. Therefore, PDE4 inhibitors might be further developed as potential antifibrotic therapies for patients with SSc. Our findings suggest that particularly patients with inflammation-driven fibrosis might benefit from PDE4 blockade.
Interleukin-17-producing T cells, besides dendritic cells, keratinocytes and neutrophils, play an important role in psoriasis biology. Contribution of CD4 T cells to disease manifestation has been investigated more in details than that of CD8 T cells, so that the role of CD8 T cells has been poorly established. In our present study, T cells were isolated from twelve lesional and non-lesional skin specimens in psoriasis patients and nine normal skin specimens from the patients undergoing skin tumor resection and skin grafting, and their phenotypical differences were compared.
In vivo models of psoriasis are needed for preclinical testing of new therapeutics, but none has adequately reflected the morphology, mRNA, and protein expression of psoriasis. Mouse models incorporating human epidermal, dermal, and immune cells have the potential to more closely reflect human psoriatic tissue. We generated human skin 3D cultures which were grafted onto NSG mice, leading to ≥80% graft acceptance and 10% contraction compared to ≤50% graft take and 60% contraction observed in nude mice.
Authors: Jang S, Kim IS, Youn SW Abstract Graft-versus-host disease (GVHD) is a common complication of bone marrow transplantation (BMT) that can be classified as acute or chronic. Chronic GVHD, which usually occurs more than 3 months after BMT, includes typical lichenoid or sclerodermatous lesions. Psoriasiform eruption is a rare clinical manifestation of chronic GVHD, and there have been no reports of psoriasiform chronic GVHD associated with hemophagocytic lymphohistiocytosis. A 33-year-old woman who was diagnosed with hemophagocytic lymphohistiocytosis 10 years ago visited our outpatient clinic with psoriasifor...
Pityriasis rubra pilaris is an idiopathic, papulosquamous dermatological disease. It is clinically and histologically distinct from, but may resemble, psoriasis. Pityriasis rubra pilaris can be self-limiting but may also run a protracted, relapsing course. Medical treatment may involve topical emollients, systemic retinoids, methotrexate, and/or tumor necrosis factor antagonists. Ocular complications include cicatricial ectropion. The authors describe the surgical management of 3 patients with cicatricial ectropion secondary to pityriasis rubra pilaris. All patients had procedures involving skin grafts; 1 patient required ...
ConclusionWe show focal loss of K14 in the basal epidermis correlating with interface dermatitis and hair follicle involvement. Moreover, enhanced reactivity of sera of patients with atopic dermatitis with K14 suggests K14 may function as an autoantigen in ASD.
CONCLUSIONS It may be hypothesized that slanDCs identified in the skin after limb transplantation may support the local inflammatory skin reaction. PMID: 26510404 [PubMed - in process]
In conclusion, this study expands our knowledge about the metabolism of bakuchiol which will be conducive to reveal its in vivo pharmacological and toxicological material basis, in addition, UPLC/ESI-PDA-QTOF-MS coupled with MetaboLynx XS software can be adopted as a useful tool for quick detection and identification of metabolites from medicine in vivo. PMID: 26347955 [PubMed - as supplied by publisher]