The United States of America, As Represented by the Secretary, Department of Health and Human Services

Richard M Siegel

Francoise Meylan

Yun-Jeong Song

Michael J Lenardo

Francis Ka-Ming Chan

Methods and compositions for treating inflammatory or autoimmune diseases in a subject comprising blocking the interaction between DR3 and TL1A. In the methods of treating inflammatory or autoimmune disease, the inflammatory or autoimmune disease can be an autoimmune disease with a T cell component, including asthma, multiple sclerosis, rheumatoid arthritis, type 1 diabetes, graft versus host disease or inflammatory bowel disease.

Nucleic acids encoding antibodies that bind to TL1A and methods of treating inflammatory or autoimmune disease

Antibodies that bind to TL1A and methods of treating inflammatory or autoimmune disease comprising administering such antibodies

Provided are methods and compositions for treating inflammatory or autoimmune diseases in a subject comprising blocking the interaction between DR3 and TL1A. The interaction between DR3 and TL1A can be blocked by reducing expression of TL1A. The interaction between DR3 and TL1A can be blocked by administration of anti-DR3 antibodies. The interaction between DR3 and TL1A can be blocked by administration of anti-TL1A antibodies. In the methods of treating inflammatory or autoimmune disease, the inflammatory or autoimmune disease can be an autoimmune disease with a T cell component. In the methods of treating inflammatory or autoimmune disease, the inflammatory or autoimmune disease can be asthma, multiple sclerosis, rheumatoid arthritis, type 1 diabetes, graft versus host disease or inflammatory bowel disease (IBD).

The present invention provides a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD) of a TNF-like receptor. Also provided by this invention is a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD), wherein the PLAD is selected from the group consisting of: the PLAD of a TNF-R, the PLAD of p60, the PLAD of p80, the PLAD of Fas (CD95/APO-1), the PLAD of TRAIL receptors, the PLAD of LT&#x3b2;R, the PLAD of CD40, the PLAD of CD30, the PLAD of CD27, the PLAD of HVEM, the PLAD of OX40 and the PLAD of DR4. TNF-R, p60, p80, Fas, TRAIL receptor, LT&#x3b2;R, CD40, CD30, CD27, HVEM, OX40, DR4, TROY, EDAR, XEDAR, DCR3, AITR, 4-1BB, DR3, RANK, TACI, BCMA, DR6, DPG, DR5, DCR1 AND DCR2 are all members of the TNF receptor superfamily or the TNF-like receptor family. The invention also provides the PLAD for other members of the TNF receptor superfamily. The polypeptides of the present invention can be utilized to inhibit oligomerization of members of the TNF receptor superfamily. These polypeptides can also be utilized to inhibit ligand binding to members of the TNF receptor superfamily. The present invention also provides a composition comprising an inhibitor of TNF receptor oligomerization. Further provided by this invention are members of the TNF receptor superfamily that are lacking a PLAD.

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Bethesda, MD, United States of America

Richard M Siegel