Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans

G Vera, P Rivera-Munoz, V Abramowski… - … and cellular biology, 2013 - Am Soc Microbiol
G Vera, P Rivera-Munoz, V Abramowski, L Malivert, A Lim, C Bole-Feysot, C Martin…
Molecular and cellular biology, 2013Am Soc Microbiol
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 …
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.
American Society for Microbiology