Fiche publication
Date publication
janvier 2022
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien
,
Dr MUELLER Christopher
Tous les auteurs :
Camara A, Lavanant AC, Abe J, Desforges HL, Alexandre YO, Girardi E, Igamberdieva Z, Asano K, Tanaka M, Hehlgans T, Pfeffer K, Pfeffer S, Mueller SN, Stein JV, Mueller CG
Lien Pubmed
Résumé
CD169 macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169 macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169 macrophage differentiation. In the spleen, the -directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8 T cells. Taken together, the data provide evidence that CD169 macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response.
Mots clés
RANK, lymph node, lymphotoxin, macrophages, spleen
Référence
Proc Natl Acad Sci U S A. 2022 Jan 18;119(3):
