title: Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.
abstract: Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected. In particular, Cernunnos is dispensable during V(D)J recombination in lymphoid cells. Nevertheless, the viability of thymocytes is reduced in Cernunnos KO mice, owing to the chronic activation of a P53-dependent DNA damage response. This translates into a qualitative alteration of the T cell repertoire to one in which the most distal Vα and Jα segments are missing. This results in the contraction of discrete T cell populations, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, in both humans and mice.
authors.affiliation: Laboratory of Genome Dynamics in the Immune System, INSERM U768, Paris, France.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Vera
authors.forename: Paola
authors.initials: P
authors.lastname: Rivera-Munoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Abramowski
authors.forename: Laurent
authors.initials: L
authors.lastname: Malivert
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.forename: Christelle
authors.initials: C
authors.lastname: Martin
authors.forename: Benoit
authors.initials: B
authors.lastname: Florkin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: Patrick
authors.initials: P
authors.lastname: Revy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: de Villartay
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D060152:V(D)J Recombination
chemical_list: D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; D016159:Tumor Suppressor Protein p53; C519508:XLF protein, mouse; D045643:DNA Repair Enzymes