Open AccessAdministration of RANKL boosts thymic regeneration upon bone marrow transplantation
Author(s) -
Lopes Noella,
Vachon Hortense,
Marie Julien,
Irla Magali
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201607176
Subject(s) - rankl , lymphotoxin , homing (biology) , immunology , regeneration (biology) , biology , bone marrow , progenitor cell , lymphopoiesis , t cell , cancer research , stem cell , immune system , microbiology and biotechnology , receptor , ecology , biochemistry , activator (genetics)
Cytoablative treatments lead to severe damages on thymic epithelial cells ( TEC s), which result in delayed de novo thymopoiesis and a prolonged period of T‐cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation ( BMT ). Here, we show that RANK ligand ( RANKL ) is upregulated in CD 4 + thymocytes and lymphoid tissue inducer ( LT i) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor‐enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LT i cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T‐cell function recovery after BMT by controlling multiple facets of thymic regeneration.