Melanocortins are derived from post-translational processing of the pro-opiomelanocortin (POMC) precursor protein and consist of melanocyte-stimulating hormones (α-, β- and γ-MSH) and adrenocorticotropic hormone (ACTH). By interacting with and activating a family of G-protein coupled melanocortin receptors (named from MC1-R to MC5-R) they regulate important physiological functions including skin pigmentation, steroidogenesis and inflammation. Over the past years it has become evident that melanocortins and their cognate receptors are widely expressed in the cells of the immune system, thus being implicated in the regulation of both innate and adaptive immune responses. Elements of the melanocortin system are also present in organ systems such as the skin, lung and gastrointestinal tract that are in direct contact with external environment, which enables melanocortins to contribute locally to innate host defense. These properties of melanocortins have sparked interest to evaluate their therapeutic potential in various inflammatory diseases.

The goal of this research topic is to advance our understanding of the role of melanocortins and their cognate receptors in the regulation of inflammation and to open new perspectives on targeting melanocortin receptors for the treatment of inflammatory and autoimmune diseases. One of the key advantages of melanocortin receptor-targeted ligands over currently available anti-inflammatory drugs is that they do not compromise the host defence mechanisms but rather enhance e.g. antimicrobial activity of phagocytes, thereby minimizing the likelihood of serious infections related to drug therapy. Furthermore, melanocortins have the unique capacity to engage multiple cell types and mechanisms to control and resolve inflammation. On the other hand, there are significant hurdles in developing effective agonists for GPCRs such as melanocortin receptors due to desensitization of the targeted receptor and decline of the desired response in repeated administration. Consequently, we hope that this research topic could further clarify the applicability of natural and synthetic melanocortin ligands in the treatment of various inflammatory diseases and identify novel treatment approaches in this context.

In this Research Topic, we welcome Original Research, Review and Clinical Trial papers that relate to, but are not limited to, the following aspects of melanocortin biology:

• Identification and characterization of novel effects/pathways/mechanisms in the regulation of inflammation and immune responses by melanocortins
• Melanocortin receptor-targeted interventions in the management of inflammatory diseases
• Evaluation of efficacy and safety of new melanocortins receptor ligands in experimental disease models related to inflammation
• Possible applications of melanocortins and synthetic melanocortin receptor ligands in previously unexplored disease areas
• Comparison of pharmacokinetic and -dynamic properties of new melanocortin receptors ligands with endogenous ligands/prototypical melanocortin receptor agonists in the context of inflammation
• Polymorphisms of melanocortin receptor genes and their association with inflammatory traits and susceptibility to inflammatory diseases
• Melanocortins as diagnostic markers in inflammatory diseases

Topic Editor Dr. Andrew Taylor is a scientific advisor and has a sponsored research agreement with Palatin Technologies INC. Topic Editor Dr. Trinidad Montero-Melendez received research Funding and conducted consultancy work for SynAct Pharma AB and TXP Pharma AG. Topic Editor Dr. Petteri Rinne has a sponsored research agreement with Palatin Technologies, Inc.

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