TGF-beta1 null mutation leads to CD154 upregulated expression in affected tissues.
The TGF-beta1(-/-) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-beta1(-/-) mice. Heart, lung, liver, and salivary gland from TGF-beta1(-/-) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-beta1(-/-) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-beta1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.
Nakabayashi
T
T
University of Texas Health Science Center at San Antonio, Department of Medicine, 78229, USA.
Sakata
K M
KM
Sakata
A
A
Kong
L
L
Lau
C A
CA
Letterio
J J
JJ
Vela-Roch
N
N
Talal
N
N
Dang
H
H
D000818:Animals; D015551:Autoimmunity; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand; D018664:Interleukin-12