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Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation
journal contribution
posted on 2023-05-17, 07:45 authored by Ruuls, SR, Hoek, RM, Ngo, VN, McNeil, T, Lucian, LA, Janatpour, MJ, Heinrich KornerHeinrich Korner, Scheerens, H, Hessel, EM, Cyster, JG, McEvoy, LM, Sedgwick, JDMice without secreted TNF but with functional, normally regulated and expressed membrane-bound TNF (memTNFΔ/Δ mice) were created by knocking-in the uncleavable Δ1-9,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 memTNFΔ/Δ 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.
History
Publication title
ImmunityVolume
15Issue
4Pagination
533-543ISSN
1074-7613Department/School
Menzies Institute for Medical ResearchPublisher
Cell PressPlace of publication
1100 Massachusetts Ave, Cambridge, USA, Ma, 02138Repository Status
- Restricted