Absence of Rac1 and Rac3 GTPases in the nervous system hinders thymic, splenic and immune-competence development

Veronica Basso, Sara Corbetta, Sara Gualdoni, Diletta Tonoli, Pietro Luigi Poliani, Francesca Sanvito, Claudio Doglioni, Anna Mondino, Ivan de Curtis

Research output: Contribution to journalArticlepeer-review

Abstract

The nervous system influences organ development by direct innervation and the action of hormones. We recently showed that the specific absence of Rac1 in neurons (Rac1N) in a Rac3-deficient (Rac3KO) background causes motor behavioural defects, epilepsy, and premature mouse death around postnatal day 13. We report here that Rac1N/Rac3KO mice display a progressive loss of immune-competence. Comparative longitudinal analysis of lymphoid organs from control, single Rac1N or Rac3KO, and double Rac1N/Rac3KO mutant animals showed that thymus development is preserved up to postnatal day 9 in all animals, but is impaired in Rac1N/Rac3KO mice at later times. This is evidenced by a drastic reduction in thymic cell numbers. Cell numbers were also reduced in the spleen, leading to splenic tissue disarray. Organ involution occurs in spite of unaltered thymocyte and lymphocyte subset composition, and proper mature T-cell responses to polyclonal stimuli in vitro. Suboptimal thymus innervation by tau-positive neuronal terminals possibly explains the suboptimal thymic output and arrested thymic development, which is accompanied by higher apoptotic rates. Our results support a role for neuronal Rac1 and Rac3 in dictating proper lymphoid organ development, and suggest the existence of lymphoid-extrinsic mechanisms linking neural defects to the loss of immune-competence.

Original languageEnglish
Pages (from-to)1410-1419
Number of pages10
JournalEuropean Journal of Immunology
Volume41
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Immune-competence
  • Neuroimmunology
  • Neurons
  • Rac GTPases
  • Thymus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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