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We recently showed that the specific absence of Rac1 in neurons (Rac1<jats:sup>N<\/jats:sup>) in a Rac3\u2010deficient (Rac3<jats:sup>KO<\/jats:sup>) background causes motor behavioural defects, epilepsy, and premature mouse death around postnatal day 13. We report here that Rac1<jats:sup>N<\/jats:sup>\/Rac3<jats:sup>KO<\/jats:sup>mice display a progressive loss of immune\u2010competence. Comparative longitudinal analysis of lymphoid organs from control, single Rac1<jats:sup>N<\/jats:sup>or Rac3<jats:sup>KO<\/jats:sup>, and double Rac1<jats:sup>N<\/jats:sup>\/Rac3<jats:sup>KO<\/jats:sup>mutant animals showed that thymus development is preserved up to postnatal day 9 in all animals, but is impaired in Rac1<jats:sup>N<\/jats:sup>\/Rac3<jats:sup>KO<\/jats:sup>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\u2010cell responses to polyclonal stimuli in vitro. Suboptimal thymus innervation by tau\u2010positive 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\u2010extrinsic mechanisms linking neural defects to the loss of immune\u2010competence.<\/jats:p>","DOI":"10.1002\/eji.201040892","type":"journal-article","created":{"date-parts":[[2011,3,7]],"date-time":"2011-03-07T14:54:56Z","timestamp":1299509696000},"page":"1410-1419","source":"Crossref","is-referenced-by-count":3,"title":["Absence of Rac1 and Rac3 GTPases in the nervous system hinders thymic, splenic and immune\u2010competence development"],"prefix":"10.1002","volume":"41","author":[{"given":"Veronica","family":"Basso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Corbetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Gualdoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diletta","family":"Tonoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro Luigi","family":"Poliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sanvito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Doglioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Mondino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"de Curtis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,4,15]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.10.017"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0031-6997(24)01510-2","article-title":"Norepinephrine and beta 2\u2010adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo","volume":"53","author":"Kohm A. 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