RRC ID 69169
Author 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.
Title CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.
Journal Proc Natl Acad Sci U S A
Abstract 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 Cd169-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.
Volume 119(3)
Published 2022-1-18
DOI 10.1073/pnas.2108540119
PII 2108540119
PMID 35031565
PMC PMC8784161
MeSH B-Lymphocytes / immunology Lymph Nodes / immunology* Lymphotoxin beta Receptor / metabolism* Macrophages / immunology* Macrophages / metabolism* RANK Ligand / metabolism Receptor Activator of Nuclear Factor-kappa B / metabolism* Sialic Acid Binding Ig-like Lectin 1 / metabolism* Signal Transduction* Spleen / immunology* Stromal Cells / metabolism
IF 9.412
Mice RBRC06239