title: Humanized TLR7/8 expression drives proliferative multisystemic histiocytosis in C57BL/6 mice.
abstract: A humanized TLR7/TLR8 transgenic mouse line was engineered for studies using TLR7/8 ligands as vaccine adjuvants. The mice developed a spontaneous immune-mediated phenotype prior to six months of age characterized by runting, lethargy, blepharitis, and corneal ulceration. Histological examination revealed a marked, multisystemic histiocytic infiltrate that effaced normal architecture. The histological changes were distinct from those previously reported in mouse models of systemic lupus erythematosus. When the mice were crossed with MyD88-/- mice, which prevented toll-like receptor signaling, the inflammatory phenotype resolved. Illness may be caused by constitutive activation of human TLR7 or TLR8 in the bacterial artificial chromosome positive mice as increased TLR7 and TLR8 expression or activation has previously been implicated in autoimmune disease.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America; Comparative Pathology Program, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Snyder
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America; Comparative Pathology Program, University of Washington, Seattle, Washington, United States of America.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Lee
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Cathy
authors.initials: C
authors.lastname: Yam
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jaehun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Alicia
authors.initials: A
authors.lastname: Brasfield
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Lisa Phuong Anh
authors.initials: LP
authors.lastname: Nguyen
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Adeline M
authors.initials: AM
authors.lastname: Hajjar
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D056426:Genetic Loci; D005838:Genotype; D015614:Histiocytosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency; D010641:Phenotype; D012720:Severity of Illness Index; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D037502:Galectin 3; D053594:Myeloid Differentiation Factor 88; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8