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Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation

Citation

Ruuls, SR and Hoek, RM and Ngo, VN and McNeil, T and Lucian, LA and Janatpour, MJ and Korner, H and Scheerens, H and Hessel, EM and Cyster, JG and McEvoy, LM and Sedgwick, JD, Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation, Immunity, 15, (4) pp. 533-543. ISSN 1074-7613 (2001) [Refereed Article]

DOI: doi:10.1016/S1074-7613(01)00215-1

Abstract

Mice without secreted TNF but with functional, normally regulated and expressed membrane-bound TNF (memTNFÎ"/Î" mice) were created by knocking-in the uncleavable Î"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 memTNFÎ"/Î" 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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Korner, H (Professor Heinrich Korner)
ID Code:72465
Year Published:2001
Web of Science® Times Cited:214
Deposited By:Research Division
Deposited On:2011-08-26
Last Modified:2011-08-29
Downloads:0

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