Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.
Mol Cell Biol
; 33(4): 701-11, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23207905
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
DNA Repair Enzymes
/
DNA-Binding Proteins
/
Gene Knockout Techniques
/
Thymocytes
Type of study:
Qualitative_research
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell Biol
Year:
2013
Type:
Article
Affiliation country:
France