Morphea, also known as localized scleroderma, is an autoimmune chronic connective tissue disease. It is characterized by excessive collagen deposition in the dermis and/or subcutaneous tissue. The etiopathogenesis of this disease is not fully understood, with endothelial cell damage, immunological disorders, extracellular matrix disorders and factors such as infection, trauma and other autoimmune diseases being considered. As medicine advances, there is increasing evidence that genetic factors play a significant role in disease risk and progression. In addition to environmental factors and genetic predisposition, epigenetic factors may be potential triggers for morphea. Epigenetics studies changes that affect gene expression without altering the DNA sequence, such as microRNAs, long non-coding RNAs or DNA methylation. Understanding the pathogenesis of this disease is key to identifying potential new treatments. There are anecdotal reports of good therapeutic effects following the use of biological drugs such as tocilizumab, a humanized IgG monoclonal antibody; abatacept, a recombinant soluble fusion protein; JAK inhibitors, such as tofacitinib and baricitinib; and a drug used successfully in cancer treatment, imatinib, a tyrosine kinase receptor inhibitor. In this article, we aim to review up-to-date knowledge on the pathogenesis of morphea, with particular emphasis on genetic and epigenetic factors. In addition, we present the new options of morphea treatment based on several case series treated with new drugs that are potential targets for the development of therapies for this disease.

Histone deacetylases (HDACs) are a group of enzymes called “epigenetic erasers”. They remove the acetyl group from histones changing the condensation state of chromatin, leading to epigenetic modification of gene expression and various downstream effects. Eighteen HDACs have been identified and grouped into four classes. The role of HDACs in T-cells has been extensively studied, and it has been proven that many of them are important players in T-cell development and function. In this review, we present the current state of knowledge on the role of HDACs in the early stages of T-cell development but also in the functioning of mature lymphocytes on the periphery, including activation, cytokine production, and metabolism regulation.

Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular processes. To date, the expression of the TMEM244 protein has not been experimentally confirmed, and its function has not been clarified. Recently, the expression of the TMEM244 gene was acknowledged to be a diagnostic marker for Sézary syndrome, a rare cutaneous T-cell lymphoma (CTCL). In this study, we aimed to determine the role of the TMEM244 gene in CTCL cells. Two CTCL cell lines were transfected with shRNAs targeting the TMEM244 transcript. The phenotypic effect of TMEM244 knockdown was validated using green fluorescent protein (GFP) growth competition assays and AnnexinV/7AAD staining. Western blot analysis was performed to identify the TMEM244 protein. Our results indicate that TMEM244 is not a protein-coding gene but a long non-coding RNA (lncRNA) that is necessary for the growth of CTCL cells.

The skin is one of the largest organs in humans and is formed by a layer (termed the epidermis) that enables the body to interact with the environment and protects it from various harmful agents. The epidermis includes a physical, biochemical, and adaptive immune barrier. The immune system in the human body is responsible for protecting organisms from potentially infectious microorganisms, allergens, and toxins, maintaining homeostasis, controlling inflammation processes, and tissue repair. Autoimmune and autoinflammatory diseases are of the immune system manifesting as aberrations in adaptive and innate immunity that lead to an inflammatory state and self-attack damage, also in the skin. The commonness of cutaneous autoinflammations has increased over the past decades, and the occurrence of the disease can have a crucial impact on a patient’s quality of life due to their visible nature, discomfort caused by somatic symptoms, and emotional and social challenges. In this review, we summarize the current knowledge of four common autoinflammatory skin diseases—vitiligo, alopecia areata, systemic lupus erythematosus, and psoriasis—with particular emphasis on their molecular background, including the role of genetic susceptibility, epigenetic regulation, and immunological pathways.