Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane).
Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas. Dendritic cells from TMPD lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.
Division of Rheumatology and Clinical Immunology, University of Florida, PO Box 100221, Gainesville, FL 32610-0221, USA.
Dina C
DC
Nacionales
Kindra M
KM
Kelly
Pui Y
PY
Lee
Haoyang
H
Zhuang
Yi
Y
Li
Jason S
JS
Weinstein
Eric
E
Sobel
Yoshiki
Y
Kuroda
Jun
J
Akaogi
Minoru
M
Satoh
Westley H
WH
Reeves
D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D002828:Choristoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006099:Granuloma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis; D007370:Interferon Type I / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000473:pathology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008899:Mineral Oil; D064547:Myxovirus Resistance Proteins; D010537:Peritoneum; D013729:Terpenes; D014452:Ubiquitins / Q000096:biosynthesis
D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; C489550:G1p2 protein, mouse; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D013729:Terpenes; D014452:Ubiquitins; D018664:Interleukin-12; C009042:pristane; D008899:Mineral Oil; D019204:GTP-Binding Proteins