Development of autoimmunity in IL-14alpha-transgenic mice.
Multiple genetic loci contribute to the development of systemic lupus erythematosus (SLE). In murine models for SLE, various genes on chromosome four have been implicated. IL-14 is a cytokine originally identified as a B cell growth factor. The il14 gene is located on chromosome 4. IL-14alpha is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10. The expression of IL-14alpha is increased in (NZB x NZW)F1 mice. In this study, we produced IL-14alpha-transgenic mice to study the role of IL-14alpha in the development of autoimmunity. At age 3-9 mo, IL-14alpha-transgenic mice demonstrate increased numbers of B1 cells in the peritoneum, increased serum IgM, IgG, and IgG 2a and show enhanced responses to T-dependent and T-independent Ags compared with littermate controls. At age 9-17 mo, IL-14alpha-transgenic mice develop autoantibodies, sialadenitis, as in Sjögren's syndrome, and immune complex-mediated nephritis, as in World Health Organization class II SLE nephritis. Between the ages 14-18 mo, 95% of IL-14alpha-transgenic mice developed CD5+ B cell lymphomas, consistent with the lymphomas seen in elderly patients with Sjögren's syndrome and SLE. These data support a role for IL-14alpha in the development of both autoimmunity and lymphomagenesis. These studies may provide a genetic link between these often related disorders.
Shen
Long
L
Division of Allergy, Immunology and Rheumatology, Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14203, USA.
Zhang
Chongjie
C
Wang
Tao
T
Brooks
Stephen
S
Ford
Richard J
RJ
Lin-Lee
Yen Chiu
YC
Kasianowicz
Amy
A
Kumar
Vijay
V
Martin
Lisa
L
Liang
Ping
P
Cowell
John
J
Ambrus
Julian L
JL
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000473:pathology; D005091:Exons; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008223:Lymphoma / Q000209:etiology* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010537:Peritoneum / Q000276:immunology; D018123:Receptors, Interleukin / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology*
D007136:Immunoglobulins; D018123:Receptors, Interleukin; C488100:TXLNA protein, human; D033921:Vesicular Transport Proteins; C094343:interleukin-14 receptor