A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: genetic evidence of synergism with lymphotoxin beta.
Lymphotoxin alpha (LTalpha) signals via tumor necrosis factor receptors (TNFRs) as a homotrimer and via lymphotoxin beta receptor (LTbetaR) as a heterotrimeric LTalpha1beta2 complex. LTalpha-deficient mice lack all lymph nodes (LNs) and Peyer's patches (PPs), and yet LTbeta-deficient mice and TNFR-deficient mice have cervical and mesenteric LN. We now show that mice made deficient in both LTbeta and TNFR type 1 (TNFR1) lack all LNs, revealing redundancy or synergism between TNFR1 and LTbeta, acting presumably via LTbetaR. A complete lack of only PPs in mice heterozygous for both ltalpha and ltbeta, but not ltalpha or ltbeta alone, suggests a similar two-ligand phenomenon in PP development and may explain the incomplete lack of PPs seen in tnfr1-/- mice.
Koni
P A
PA
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Flavell
R A
RA
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018628:Gene Dosage; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008643:Mesentery / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha