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.
Highlights
Secondary lymphoid organs such as lymph nodes and spleen are essential sentinels against invading pathogens and developing tumors [1, 2]
In WT ! lymphotoxin β-receptor (LTβR)-/- splenic regenerates the size of the red pulp was increased, whereas the size of the marginal zone and that of the B- and T-cell zones was similar to that of a normal WT spleen (Fig 3A)
RORγt which is preferentially expressed by lymphoid tissue inducer cells [42] could not be detected in normal WT spleens (7 out of 7) whereas a detectable amount of transcript was present in 4 out of 7 WT ! LTβR-/- splenic regenerates indicating that process of splenic tissue regeneration was still going on
Summary
Secondary lymphoid organs such as lymph nodes and spleen are essential sentinels against invading pathogens and developing tumors [1, 2]. The lymphotoxin β-receptor (LTβR) pathway is involved in the export of T cells from the thymus [7], but is one of the main regulators of secondary lymphoid organ formation [8, 9, 10, 11]. It is PLOS ONE | DOI:10.1371/journal.pone.0166901 December 9, 2016
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