Objective. The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibodymediated immune response that leads to SLE skin lesions.Methods. The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay.Results. We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. Conclusion. Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.Systemic lupus erythematosus (SLE) is a unique autoimmune disease characterized by extremely heterogeneous clinical manifestations and the most complex autoantibody profile (1-5). Autoantibodies not only serve as a marker of disease diagnosis, activity, and severity (6,7), but they also play a primary and pivotal role in the initiation and exacerbation of SLE disease (8,9). A cluster of anti-nuclear debris antibodies, including anti-double-stranded DNA (anti-dsDNA), anti-

A Western diet (WD)-characterized by its high fat and simple sugar content-is thought to predispose individuals to inflammatory skin diseases such as psoriasis through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to T helper type 1e/T helper type 17ebiased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with a WD promoted mild dermatitis and accumulation of IL-17Aeproducing gd T cells in the skin. Strikingly, gd T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased the potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRdedeficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of gd T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and bile acid pathways may be key to the development of WD-associated psoriasiform dermatitis.

A B S T R A C TBackground: Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood. Objective: To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice. Methods: Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions. Results: Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45 + leukocytes, mast cells as well as CD3 + T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice. Conclusions: In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.

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Tumor-associated macrophages (TAMs) recruited from blood monocytes are key in establishing an immunosuppressive tumor microenvironment (TME) for the support of tumor growth. We hypothesize that blocking monocyte trafficking (through the inhibition of specific chemokine receptors) into skin can positively affect tumor development. Herein, the authors examined the effects of oral administration of a small molecule inhibitor for CCR2, CCR2i, which blocks CCR2-mediated chemotaxis of monocytes in a syngeneic mouse T-cell lymphoma in skin. Following CCR2i administration, the depletion of macrophages was achieved as early as 2 days after tumor initiation in ear TME. Quantitative real-time PCR detected an increase in the levels of immune stimulatory inflammatory cytokines, for example, IFN-g and IL-12, in CCR2i-versus vehicle-treated mice. Within 2 weeks, the tumors from the control groups attained the maximum size, whereas CCR2i-treated mice exhibited much smaller tumor sizes and weights. Immunohistochemistry revealed that CCR2i-treated tumors possessed considerably more CD8þ T cells, which demonstrated their essential role in CCR2i-induced tumor inhibition. Finally, the combination of anti-programmed cell death protein 1 with CCR2i considerably increased the efficacy of tumor eradication related to the activation of IFN-geproducing CD8 T cells. Our findings provide strong evidence that the CCR2i, particularly in combination with an immune checkpoint inhibitor, reduces tumor growth and is a potential future treatment option for cutaneous T-cell lymphomas.

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Anti-P antibody is significantly associated with malar rash, oral ulcer, photosensitivity and serum anti-dsDNA antibody, and potentially associated with NPSLE, hepatic damage, serum anti-Sm and aCL.