title: Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation.
abstract: Mice without secreted TNF but with functional, normally regulated and expressed membrane-bound TNF (memTNF(Delta/Delta) mice) were created by knocking-in the uncleavable Delta 1-9,K11E TNF allele. In contrast to TNF-deficient mice (TNF(-/-)), memTNF supported many features of lymphoid organ structure, except generation of primary B cell follicles. Splenic chemokine expression was near normal. MemTNF-induced apoptosis was mediated through both TNF-R1 and TNF-R2. That memTNF is suboptimal for development of inflammation was revealed in experimental autoimmune encephalomyelitis. Disease severity was reduced in memTNF(Delta/Delta) mice relative to wild-type mice, and the nature of spinal cord infiltrates resembled that in TNF(-/-) mice. We conclude that memTNF supports many processes underlying lymphoid tissue structure, but secreted TNF is needed for optimal inflammatory lesion development.
authors.affiliation: DNAX, 901 California Avenue, Palo Alto, CA 94304, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Ruuls
authors.forename: R M
authors.initials: RM
authors.lastname: Hoek
authors.forename: V N
authors.initials: VN
authors.lastname: Ngo
authors.forename: T
authors.initials: T
authors.lastname: McNeil
authors.forename: L A
authors.initials: LA
authors.lastname: Lucian
authors.forename: M J
authors.initials: MJ
authors.lastname: Janatpour
authors.forename: H
authors.initials: H
authors.lastname: Körner
authors.forename: H
authors.initials: H
authors.lastname: Scheerens
authors.forename: E M
authors.initials: EM
authors.lastname: Hessel
authors.forename: J G
authors.initials: JG
authors.lastname: Cyster
authors.forename: L M
authors.initials: LM
authors.lastname: McEvoy
authors.forename: J D
authors.initials: JD
authors.lastname: Sedgwick
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D018390:Gene Targeting; D018858:Germinal Center / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D017384:Sequence Deletion; D012769:Shock / Q000209:etiology; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha