Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin ?-Receptor Signaling (LT?R) 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 ?-receptor (LT?R) signaling. It is unclear, however, by which molecular mechanism their size is limited. Here, we investigate whether the LT?R pathway is also growth suppressing. By using splenic tissue transplantation it is possible to analyze a potential contribution of LT?R signaling inside and outside of the implanted tissue. We show that LT?R 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 LT?R expressing cells in the animal (regenerate weights of 115 ± 8 mg in LT?R deficient recipients and of 12 ± 9 mg in wild-type recipients), affected also developed splenic tissue, and was induced but not executed via LT?R signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LT?R dependent suppressive activity. Thus, LT?R 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.

SUBMITTER: Milicevic NM 

PROVIDER: S-EPMC5147843 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature