An extraribosomal function of ribosomal protein L13a in macrophages resolves inflammation

J Immunol. 2013 Apr 1;190(7):3600-12. doi: 10.4049/jimmunol.1201933. Epub 2013 Mar 4.


Inflammation is an obligatory attempt of the immune system to protect the host from infections. However, unregulated synthesis of proinflammatory products can have detrimental effects. Although mechanisms that lead to inflammation are well appreciated, those that restrain it are not adequately understood. Creating macrophage-specific L13a-knockout mice, we report that depletion of ribosomal protein L13a abrogates the endogenous translation control of several chemokines in macrophages. Upon LPS-induced endotoxemia, these animals displayed symptoms of severe inflammation caused by widespread infiltration of macrophages in major organs causing tissue injury and reduced survival rates. Macrophages from these knockout animals show unregulated expression of several chemokines (e.g., CXCL13, CCL22, CCL8, and CCR3). These macrophages failed to show L13a-dependent RNA binding complex formation on target mRNAs. In addition, increased polyribosomal abundance of these mRNAs shows a defect in translation control in the macrophages. Thus, to our knowledge, our studies provide the first evidence of an essential extraribosomal function of ribosomal protein L13a in resolving physiological inflammation in a mammalian host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endotoxemia / genetics
  • Endotoxemia / immunology
  • Endotoxemia / pathology
  • Endotoxins / metabolism
  • Female
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Homozygote
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Organ Specificity / genetics
  • Peritoneum / immunology
  • Peritoneum / pathology
  • Protein Biosynthesis / genetics
  • Response Elements
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Spleen / immunology
  • Spleen / pathology


  • Endotoxins
  • Ribosomal Proteins
  • Rpl13a protein, mouse