Experimental Models of Lupus Erythematosus

Furukawa, Fukumi

doi:10.1007/3-540-26581-3_16

Cited by 4 publications

(5 citation statements)

References 83 publications

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“…Confocal microscopy revealed that the IgG‐fractionated anti‐SS‐A/Ro antibodies bound to the surface of the keratinocytes, which was compatible with our recent report [26].…”

Section: Resultssupporting

confidence: 92%

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Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Furukawa

Itoh

Wakita

et al. 1999

Clinical and Experimental Immunology

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SUMMARYKeratinocyte cytotoxicity is an important component of the immunopathology of photosensitive lupus erythematosus, and antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be an important mechanism by which autoantibodies, especially those specific for SS-A/Ro, can induce keratinocyte damage in models of photosensitive lupus. We provide further evidence that keratinocytes from patients with photosensitive lupus show significantly greater ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets is especially enhanced by autologous patient's serum or by anti-SS-A/Ro þ sera. Keratinocytes from normal uninvolved skin of 29 patients with cutaneous lupus erythematosus (LE) were grown in cell culture and tested as targets in cytotoxicity experiments in vitro. Cultured keratinocytes from patients with systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE) showed significantly greater cytotoxicity following UVR treatment than did keratinocytes from normal adult controls or from neonatal foreskins (P < 0·01). The same cultures also showed greater UVR-induced binding of IgG from fractionated anti-SS-A/Ro þ preparations. ADCC experiments were also performed using keratinocytes cultured from patients with SLE, SCLE, discoid lupus erythematosus (DLE), and normal controls. When keratinocytes were incubated in autologous serum plus a standard mononuclear cell effector population, the percentage of ADCC observed was significantly greater in cultures containing keratinocytes and sera from the SLE and SCLE patients (P < 0·001). When cultured keratinocytes were added to different IgG antibody probes, plus standard mononuclear effector populations, greater ADCC was seen using the anti-SS-A/Ro probe and keratinocytes from patients with SLE or SCLE. With normal human neonatal keratinocyte targets, the anti-SS-A/Ro probe induced greater ADCC than that seen with anti-ssDNA or normal human serum. We have shown that keratinocytes from patients with some forms of lupus erythematosus (SLE and SCLE) show greater cytotoxicity in vitro when irradiated with UVR, and greater susceptibility to ADCC whether the antibody source is their own serum or an anti-SS-A/Ro probe.

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“…Confocal microscopy revealed that the IgG‐fractionated anti‐SS‐A/Ro antibodies bound to the surface of the keratinocytes, which was compatible with our recent report [26].…”

Section: Resultssupporting

confidence: 92%

“…Confocal microscopic assessment of the localization was also analysed by a BioRad MRC600 (Cambridge, MA) equipped with an argon ion laser exciting maximally at 488 nm and 514 nm, and was controlled by CoMoS software [25, 26]. Cell surface binding of IgG was demonstrated by confocal microscopy [26], confirming many previous reports [5,9–13].…”

Section: Methodssupporting

confidence: 54%

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Furukawa

Itoh

Wakita

et al. 1999

Clinical and Experimental Immunology

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“…At the 12th generation of MRL mice inbreeding, a sub-strain with a spontaneous mutation in the lpr gene (which is located on chromosome 19 and encodes the FAS receptor) emerged; by cross-mating these mice, a lpr-mutated homozygous mouse strain (namely, MRL/lpr mouse) was obtained. This murine model displays a SLE-like phenotype with a shorter survival, compared to the NZB/W F1 strain and, notably, does not show any gender bias for the lupus-like phenotype [18][19][20].…”

Section: Dnt Cells and Lupus In Micementioning

confidence: 79%

Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus

Poddighe,

Dossybayeva,

Kozhakhmetov

et al. 2024

Biomedicines

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Double-negative T (DNT) cells are a rare and unconventional T-lymphocyte subpopulation lacking both CD4 and CD8 markers. Their immunopathological roles and clinical relevance have yet to be elucidated. Beyond autoimmune lymphoproliferative syndrome (ALPS), these cells may also play a role in rheumatic disorders, including systemic lupus erythematosus (SLE); indeed, these two diseases share several autoimmune manifestations (including nephritis). Moreover, one of the main experimental murine models used to investigate lupus, namely the MRL/lpr mouse, is characterized by an expansion of DNT cells, which can support the production of pathogenic autoantibodies and/or modulate the immune response in this context. However, lupus murine models are not completely consistent with their human SLE counterpart, of course. In this mini review, we summarize and analyze the most relevant clinical studies investigating the DNT cell population in SLE patients. Overall, based on the present literature review and analysis, DNT cell homeostasis seems to be altered in patients with SLE. Indeed, most of the available clinical studies (which include both adults and children) reported an increased DNT cell percentage in SLE patients, especially during the active phases, even though no clear correlation with disease activity and/or inflammatory parameters has been clearly established. Well-designed, standardized, and longitudinal clinical studies focused on DNT cell population are needed, in order to further elucidate the actual contribution of these cells in SLE pathogenesis and their interactions with other immune cells (also implicated and/or altered in SLE, such as basophils), and clarify whether their expansion and/or immunophenotypic aspects may have any immunopathological relevance (and, then, represent potential disease markers and, in perspective, even therapeutic targets) or are just an unspecific epiphenomenon of autoimmunity.

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“…The promotion of skin lesions in MRL/lpr mice by UVB exposure may not be associated with the acceleration of intrinsic SLE phenomena, but rather with reactive changes of the skin against environmental stimuli [6,8]. Like the susceptible UV-induced cytotoxicity observed in fibroblasts from NZB mice [16], fibroblasts and keratinocytes cultured from MRL/lpr mice are susceptible to UVB-induced cytotoxicity, which was associated with intrinsic SLE phenomena, and might be regulated by the individual's genetic background [9,13].…”

Section: Sle-prone Micementioning

confidence: 88%

“…With regard to experimental autoimmune diseases, these models can be divided into several broad groups (Table 2) [8,9]. Historically, Natali and Tan [10] reported that mice immunized with UV-irradiated DNA showed skin lesions that clinically and immunohistologically resembled the skin lesions of human SLE after receiving whole-body UV-irradiation.…”

Section: Mouse Modelsmentioning

confidence: 98%