title: Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues.
abstract: Development and maintenance of secondary lymphoid organs such as lymph nodes and spleen essentially depend on lymphotoxin β-receptor (LTβR) signaling. It is unclear, however, by which molecular mechanism their size is limited. Here, we investigate whether the LTβR pathway is also growth suppressing. By using splenic tissue transplantation it is possible to analyze a potential contribution of LTβR signaling inside and outside of the implanted tissue. We show that LTβR signaling within the endogenous spleen and within non-splenic tissues both significantly suppressed the regeneration of implanted splenic tissue. The suppressive activity positively correlated with the total number of LTβR expressing cells in the animal (regenerate weights of 115 ± 8 mg in LTβR deficient recipients and of 12 ± 9 mg in wild-type recipients), affected also developed splenic tissue, and was induced but not executed via LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size of secondary lymphoid organs, and might be therapeutically used to eradicate tertiary lymphoid tissues during autoimmune diseases.
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Beograd, Beograd, Serbia.
authors.forename: Novica M
authors.initials: NM
authors.lastname: Milićević
authors.affiliation: Department I of Anatomy, University of Cologne, Cologne, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Nohroudi
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Lübeck, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Lübeck, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Lübeck, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Ringer
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Beograd, Beograd, Serbia.
authors.forename: Živana
authors.initials: Ž
authors.lastname: Milićević
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Lübeck, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000254:growth & development / Q000378:metabolism* / Q000637:transplantation; D013156:Splenectomy; D017154:Stromal Cells / Q000378:metabolism; D016378:Tissue Transplantation / Q000379:methods*
chemical_list: D002352:Carrier Proteins; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D020381:Interleukin-17; D053259:Lymphotoxin beta Receptor; C000600072:MFAP4 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3