A crucial role for HVEM and BTLA in preventing intestinal inflammation.
The interaction between the tumor necrosis factor (TNF) family member LIGHT and the TNF family receptor herpes virus entry mediator (HVEM) co-stimulates T cells and promotes inflammation. However, HVEM also triggers inhibitory signals by acting as a ligand that binds to B and T lymphocyte attenuator (BTLA), an immunoglobulin super family member. The contribution of HVEM interacting with these two binding partners in inflammatory processes remains unknown. In this study, we investigated the role of HVEM in the development of colitis induced by the transfer of CD4(+)CD45RB(high) T cells into recombination activating gene (Rag)(-/-) mice. Although the absence of HVEM on the donor T cells led to a slight decrease in pathogenesis, surprisingly, the absence of HVEM in the Rag(-/-) recipients led to the opposite effect, a dramatic acceleration of intestinal inflammation. Furthermore, the critical role of HVEM in preventing colitis acceleration mainly involved HVEM expression by radioresistant cells in the Rag(-/-) recipients interacting with BTLA. Our experiments emphasize the antiinflammatory role of HVEM and the importance of HVEM expression by innate immune cells in preventing runaway inflammation in the intestine.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Marcos W
MW
Steinberg
Olga
O
Turovskaya
Raziya B
RB
Shaikh
Gisen
G
Kim
Declan F
DF
McCole
Klaus
K
Pfeffer
Kenneth M
KM
Murphy
Carl F
CF
Ware
Mitchell
M
Kronenberg
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000502:physiology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
C488868:BTLA protein, mouse; D018398:Homeodomain Proteins; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse; C064658:RAG-1 protein