Human Translational Research in Psoriasis Using CLA+ T Cells

Focusing on the study of human memory CLA+ T cells to understand psoriasis pathology constitutes an innovative approach to explore the pathological mechanism of this chronic cutaneous inflammatory disease. CLA+ T cells can be considered peripheral cell biomarkers in the study of T-cell mediated human skin diseases. During the last few years, new evidences have been found that link streptococcal infection with IL-17 response in psoriasis by studying the interaction between Streptococcus pyogenes with CLA+ T cells and autologous epidermal cells. S. pyogenes constitutes the best clinically characterized trigger of psoriasis and by exploring its effect on CLA+ T cells and epidermal cells in psoriasis may allow understanding psoriasis by using patient’s clinical samples ex vivo

Pathological Mechanisms of Skin Homing T Cells in Atopic Dermatitis

Skin infiltration of circulating memory T cells with cutaneous tropism is considered one of the pathologic mechanisms in atopic dermatitis (AD). Skin-seeking circulating T lymphocytes can be identified by their expression of the cutaneous lymphocyte-associated antigen on the cell surface. Recent studies have contributed useful new information about the function and recirculation properties of those cells in AD patients. This review integrates the latest findings on peripheral cutaneous lymphocyte-associated antigen memory T cells in AD and highlights the relevance of this cell type and its importance to our understanding of the pathologic mechanisms of AD. Keywords: homing, CLA, skin, atopic eczema, T cel

Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation

MCPIP1 (Regnase-1, encoded by the ZC3H12A gene) regulates the mRNA stability of several inflammatory cytokines. Due to the critical role of this RNA endonuclease in the suppression of inflammation, Mcpip1 deficiency in mice leads to the development of postnatal multiorgan inflammation and premature death. Here, we generated mice with conditional deletion of Mcpip1 in the epidermis (Mcpip1(EKO)). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflammation and keratinocyte differentiation, such as IL-36 alpha/gamma cytokines, S100a8/a9 antibacterial peptides, and Sprr2d/2h proteins. Upon aging, the Mcpip1(EKO) mice showed impaired skin integrity that led to the progressive development of spontaneous skin pathology and systemic inflammation. Furthermore, we found that the lack of epidermal Mcpip1 expression impaired the balance of keratinocyte proliferation and differentiation. Overall, we provide evidence that keratinocyte-specific Mcpip1 activity is crucial for the maintenance of skin integrity as well as for the prevention of excessive local and systemic inflammation. Key messages Loss of murine epidermal Mcpip1 upregulates transcripts related to inflammation and keratinocyte differentiation. Keratinocyte Mcpip1 function is essential to maintain the integrity of skin in adult mice. Ablation of Mcpip1 in mouse epidermis leads to the development of local and systemic inflammation