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Antinuclear autoantibodies and lupus nephritis in transgenic mice expressing interferon gamma in the epidermis.

Seery JP, Carroll JM, Cattell V, Watt FM - J. Exp. Med. (1997)

Bottom Line: The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) gamma plays a key role.There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones.Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-gamma, in the pathogenesis of SLE.

View Article: PubMed Central - PubMed

Affiliation: Keratinocyte Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.

ABSTRACT
Systemic lupus erythematosus (SLE) is a potentially fatal non-organ-specific autoimmune disease that predominantly affects women. Features of the disease include inflammatory skin lesions and widespread organ damage caused by deposition of anti-dsDNA autoantibodies. The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) gamma plays a key role. We have used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis. There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones. Autoantibody levels in female mice were significantly higher than in male transgenic mice. Furthermore, there was IgG deposition in the glomeruli of all female mice and histological evidence of severe proliferative glomerulonephritis in a proportion of these animals. Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-gamma, in the pathogenesis of SLE.

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Indirect immunofluorescence staining of cultured (A and B)  mouse and (C) human keratinocytes. (A and C) Stained with serum from  a transgenic mouse (diluted 1:10). (B) Stained with antidesmoglein antibody. Scale bar (A and B): 30 μm; (C): 60 μm.
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Figure 1: Indirect immunofluorescence staining of cultured (A and B) mouse and (C) human keratinocytes. (A and C) Stained with serum from a transgenic mouse (diluted 1:10). (B) Stained with antidesmoglein antibody. Scale bar (A and B): 30 μm; (C): 60 μm.

Mentions: Autoantibodies directed against membrane antigens are a feature of several autoimmune skin diseases, the antigens frequently being proteins involved in cell–cell or cell–extracellular matrix adhesion (19, 20). The cellular distribution of the antigens recognized by antibodies in the serum of the IFN-γ transgenic mice was examined by staining cultured mouse and human keratinocytes (Fig. 1, A and C). In the 10 serum samples examined (Table 1) there was intense staining of the nucleus, with no evidence of membrane staining. Autoantibodies stained nuclei of both mouse and human cells. For comparison, keratinocytes were stained with an antibody to desmogleins, the autoantigens of pemphigus vulgaris and pemphigus foliaceus; as illustrated in Fig. 1 B the staining pattern was quite distinct from that observed with autoantibodies from the IFN-γ transgenic mice.


Antinuclear autoantibodies and lupus nephritis in transgenic mice expressing interferon gamma in the epidermis.

Seery JP, Carroll JM, Cattell V, Watt FM - J. Exp. Med. (1997)

Indirect immunofluorescence staining of cultured (A and B)  mouse and (C) human keratinocytes. (A and C) Stained with serum from  a transgenic mouse (diluted 1:10). (B) Stained with antidesmoglein antibody. Scale bar (A and B): 30 μm; (C): 60 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199116&req=5

Figure 1: Indirect immunofluorescence staining of cultured (A and B) mouse and (C) human keratinocytes. (A and C) Stained with serum from a transgenic mouse (diluted 1:10). (B) Stained with antidesmoglein antibody. Scale bar (A and B): 30 μm; (C): 60 μm.
Mentions: Autoantibodies directed against membrane antigens are a feature of several autoimmune skin diseases, the antigens frequently being proteins involved in cell–cell or cell–extracellular matrix adhesion (19, 20). The cellular distribution of the antigens recognized by antibodies in the serum of the IFN-γ transgenic mice was examined by staining cultured mouse and human keratinocytes (Fig. 1, A and C). In the 10 serum samples examined (Table 1) there was intense staining of the nucleus, with no evidence of membrane staining. Autoantibodies stained nuclei of both mouse and human cells. For comparison, keratinocytes were stained with an antibody to desmogleins, the autoantigens of pemphigus vulgaris and pemphigus foliaceus; as illustrated in Fig. 1 B the staining pattern was quite distinct from that observed with autoantibodies from the IFN-γ transgenic mice.

Bottom Line: The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) gamma plays a key role.There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones.Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-gamma, in the pathogenesis of SLE.

View Article: PubMed Central - PubMed

Affiliation: Keratinocyte Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.

ABSTRACT
Systemic lupus erythematosus (SLE) is a potentially fatal non-organ-specific autoimmune disease that predominantly affects women. Features of the disease include inflammatory skin lesions and widespread organ damage caused by deposition of anti-dsDNA autoantibodies. The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) gamma plays a key role. We have used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis. There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones. Autoantibody levels in female mice were significantly higher than in male transgenic mice. Furthermore, there was IgG deposition in the glomeruli of all female mice and histological evidence of severe proliferative glomerulonephritis in a proportion of these animals. Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-gamma, in the pathogenesis of SLE.

Show MeSH
Related in: MedlinePlus