title: TNF receptor-1 is required for the formation of splenic compartments during adult, but not embryonic life.
abstract: Lymphotoxin β-receptor (LTβR) and TNF receptor-1 (TNFR1) are important for the development of secondary lymphoid organs during embryonic life. The significance of LTβR and TNFR1 for the formation of lymphoid tissue during adult life is not well understood. Immunohistochemistry, morphometry, flow cytometry, and laser microdissection were used to compare wild-type, LTβR(-/-), TNFR1(-/-) spleens with splenic tissue that has been newly formed 8 wk after avascular implantation into adult mice. During ontogeny, LTβR is sufficient to induce formation of the marginal zone, similar-sized T and B cell zones, and a mixed T/B cell zone that completely surrounded the T cell zone. Strikingly, in adult mice, the formation of splenic compartments required both LTβR and TNFR1 expression, demonstrating that the molecular requirements for lymphoid tissue formation are different during embryonic and adult life. Thus, interfering with the TNFR1 pathway offers the possibility to selectively block the formation of ectopic lymphoid tissue and at the same time to spare secondary lymphoid organs such as spleen and lymph nodes. This opens a new perspective for the treatment of autoimmune and inflammatory diseases.
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Beograd, 11000 Beograd, Serbia.
authors.forename: Novica M
authors.initials: NM
authors.lastname: Milićević
authors.forename: Karola
authors.initials: K
authors.lastname: Klaperski
authors.forename: Klaus
authors.initials: K
authors.lastname: Nohroudi
authors.forename: Živana
authors.initials: Ž
authors.lastname: Milićević
authors.forename: Katja
authors.initials: K
authors.lastname: Bieber
authors.forename: Babett
authors.initials: B
authors.lastname: Baraniec
authors.forename: Maike
authors.initials: M
authors.lastname: Blessenohl
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000375:Aging / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002451:Cell Compartmentation / Q000276:immunology; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D053259:Lymphotoxin beta Receptor; D047888:Receptors, Tumor Necrosis Factor, Type I