Immune System/ Bone/ Fat cross-talk: the role of LIGHT/ TNFSF14

Abstract

LIGHT/TNFS14 is a cytokine produced by immune cells. We demonstrated its role in regulating basal and pathological bone remodeling whereas other authors showed its pro-adi- pogenic role. Based on the “immune system/bone/fat” cross-talk, in this study we investigat- ed whether LIGHT could be a new linker of this interaction. In bone marrow cell extracts of Tnfsf14-/- mice (KO), in which we proved the reduced trabecular bone, here we firstly detected a reduced expression of PPARγ, the key pro-adipogenic transcription factor. Consistently, we detected a lower weight of visceral and inguinal white adipose (iWAT) tissues respect to the WT mice, suggesting an impairment of adipocyte precursors in LIGHT deficient mice. Moreo- ver, in the iWAT of these mice, we detected a lower number of brown adipocytes and lower mRNA levels of Wnt10b, involved in browning response, respect to WT mice, indicating that LIGHT-deficiency alters the adipose phenotype together with the bone one. These effects are mediated by immune cells, indeed, by using Rag-/Tnfsf14-mice lacking mature B/T-cells and LIGHT expression, the levels of PPARγ in bone marrow extracts and the number of brown adi- pocytes in iWAT are rescued respect to KO mice. These findings indicate LIGHT as new linker in immune system/bone/fat cross-talk and a potential target in obesity.