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Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. The inflammatory microenvironment in mycosis fungoides is complex. There is accumulating evidence that the neoplastic T-cells take control of the microenvironment and thereby promote their own expansion by suppressing cellular immunity. B-cells have proved to be upregulated in large-cell transformed mycosis fungoides, and could potentially play a role in disease progression. To investigate the presence of B-cells in mycosis fungoides compared with controls, this study analysed 85 formalin-fixed and paraffin-embedded mycosis fungoides biopsies. MS4A1 gene expression was significantly upregulated in mycosis fungoides compared with controls (p < 0.0001) and further upregulated in disease progression, (p = 0.001). Digital quantification of PAX5+/CD20+ cells confirmed the increased presence of Bcells in mycosis fungoides compared with controls. No co-labelling of CD3/CD20 was observed in the neoplastic T-cells. This study found a significantly increased presence of B-cells in the tumour-associated microenvironment in mycosis fungoides. These findings could potentially lead to new treatment strategies for mycosis fungoides. [ABSTRACT FROM AUTHOR]

It is difficult to distinguish erythrodermic mycosis fungoides from Sézary syndrome due to their similar clinical and histological features. The main purpose of this study was to investigate whether microRNA expression profiles in lesional skin could discriminate patients with erythrodermic mycosis fungoides from those with Sézary syndrome. A further aim was to assess whether the microRNA expression profiles in erythrodermic mycosis fungoides skin was more comparable to microRNA expression profiles of Sézary syndrome or early-stage mycosis fungoides. RNA was extracted from diagnostic skin biopsies, followed by quantitative reverse transcription polymerase chain reaction analysis of 383 microRNAs. Twenty-seven microRNAs were significantly differentially expressed between erythrodermic mycosis fungoides and Sézary syndrome. Moreover, erythrodermic mycosis fungoides showed microRNA features overlapping with Sézary syndrome and early-stage mycosis fungoides, although hierarchical cluster analysis co-clustered erythrodermic mycosis fungoides with early-stage mycosis fungoides rather than with Sézary syndrome. These findings underscore that erythrodermic mycosis fungoides and Sézary syndrome are different diseases. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, pruritic skin disease characterized by type 2 immune-mediated inflammation and skin barrier dysfunction (1). The impaired skin barrier in AD is related to decreased expression of epidermal barrier proteins and to changes in lipid composition in the stratum corneum. AD lesions are characterized by increased expression of pro-inflammatory mediators, such as chemokines, leading to recruitment of immune cells, which may further exacerbate the inflammation. Interleukin (IL)-13 and IL-4 are the signature type 2 cytokines involved in AD. These cytokines both signal through the type II receptor, composed of IL-4Ra and IL-13Ra1, and display functional redundancy in cells harbouring this receptor, including keratinocytes and fibroblasts. This is in contrast to cells, such as T lymphocytes, containing the type I receptor (IL-4Ra combined with the common gamma chain), which is only used by IL-4 for signalling. Monoclonal antibodies targeting IL-4Ra (dupilumab) or IL-13 (tralokinumab and lebrikizumab) have demonstrated clinical efficacy in AD (2-4). Interestingly, protein levels of IL-13, but not IL-4, are consistently detected and shown to be increased in AD skin across studies (5, 6). Furthermore, 3 recently published studies using RNA-sequencing of AD biopsies found increased levels of IL13 in lesional and non-lesional AD skin, whereas expression of IL4 was undetectable or very low (7-9). Independent studies also found a correlation between expression levels of IL-13 at mRNA or protein level in lesional AD skin and disease severity (6, 7). The aim of the current study is to further investigate effects of IL-13 on AD-associated genes in human skin cells and to provide molecular insights into the mechanism of action of tralokinumab, a fully human IgG4 monoclonal antibody that specifically neutralizes IL-13. [ABSTRACT FROM AUTHOR]