Myeloid-specific Deficiency of Ribosomal Protein L13a Alters Macrophage Polarity and Diversity During Differentiation from Bone Marrow

Document Type

Article

Publication Date

7-2025

Publication Title

Journal of Leukocyte Biology

Disciplines

Biology | Cell Biology

Abstract

Macrophages show substantial plasticity, leading to a diverse population of these cells with different states of polarization during differentiation from bone marrow. However, the mechanisms underlying this process are not well understood. Here, we identified a novel role of ribosomal protein L13a previously shown to be engaged in the physiological control of inflammation regulating macrophage diversity and polarity. Using an ex-vivo differentiation model of bone marrow-derived macrophages (BMDM) from the control (L13aflox/flox) and myeloid-specific L13a KO (L13aflox/flox LysMCre+) mice (L13a-KO), we present compelling evidence of the role of L13a in regulating macrophage polarization that goes beyond the M1-M2-based binary concept. We show that macrophages from L13a-KO mice lead to enhanced expression of classical markers of both M1 and M2 and surprising deviation from the expected response under known inducers of polarity. The phosphorylation-dependent activation of a number of signaling molecules played a role in this process. Bulk RNA and single-cell RNA sequencing of the BMDM from the L13a-KO mice show widespread change in overall gene expression and robust differences in the diverse populations of the bone marrow-derived cells from the control and KO mice. In addition, this study also shows a substantial increase of Th1 and Th2 signature genes in CD4+ T cells isolated from the L13a-KO animals. Together, our studies provide new insights into the regulations of macrophage polarization by L13a-driven novel intermediate effectors or mediators.

Comments

These studies are supported by National Institute of Health (NIH) grant NIHR21 AI173187 to B.M., NIHRO1 GM128981 to A.A.K., and Defense Advanced Research Projects Agency (DARPA) grant AWD00001593 to P.Jt

DOI

10.1093/jleuko/qiaf102

Volume

117

Issue

7

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