The Lymphotoxin Network: orchestrating a type I interferon response to optimize adaptive immunity.
The Lymphotoxin (LT) pathway is best known for its role in orchestrating the development and homeostasis of lymph nodes and Peyer's patches through the regulation of homeostatic chemokines. More recently an appreciation of the LTβR pathway in the production of Type I interferons (IFN-I) during homeostasis and infection has emerged. LTβR signaling is essential in differentiating stromal cells and macrophages in lymphoid organs to rapidly produce IFN-I in response to virus infections independently of the conventional TLR signaling systems. In addition, LTβR signaling is required to produce homeostatic levels of IFN-I from dendritic cells in order to effectively cross-prime a CD8+ T cell response to protein antigen. Importantly, pharmacological inhibition of LTβR signaling in mice has a profound positive impact on a number of autoimmune disease models, although it remains unclear if this efficacy is linked to IFN-I production during chronic inflammation. In this review, we will provide a brief overview of how the "Lymphotoxin Network" is linked to the IFN-I response and its impact on the immune system.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Jennifer L
JL
Gommerman
Department of Microbiology and Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USA.
Jeffrey L
JL
Browning
Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA. Electronic address: cware@sanfordburnham.org.
Carl F
CF
Ware
D056704:Adaptive Immunity; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology*; D053259:Lymphotoxin beta Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000276:immunology
D007370:Interferon Type I; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha
Autoimmunity; Dendritic cells; Interferon (IFN); Lymphotoxin-αβ (LTαβ); Stromal cells