Details

Autor(en) / Beteiligte

• Cruz, J. Agustin
• Borghesi, Lisa

Titel

DNA damage in hematopoietic stem cells as a mechanism for lymphoid progenitor exhaustion in E47 deficient mice (111.20)

Ist Teil von

• The Journal of immunology (1950), 2012-05, Vol.188 (1_Supplement), p.111-111.20

Erscheinungsjahr

2012

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Abstract Aging and chronic infection are known to cause decreases in lymphopoiesis and in early hematopoietic progenitors, ultimately manifesting as poor responsiveness to new pathogens and reduced efficacy of vaccination. However, the mechanisms involved in these manifestations are still not completely understood. E47 is a transcription factor that regulates the proliferative integrity of early hematopoietic progenitors, and chronic TLR stimulation decreases the levels of E47 in mice. Additionally, E47 KO mice develop an exhaustion of lymphoid progenitors as they age. Consequently, we hypothesize that the responsive pathway to the aging process of the immune system involves a decreased expression of E47, and increases in both cell cycling and reactive oxygen species exposure, which lead to an increase of DNA damage in hematopoietic progenitors and subsequent exhaustion. In order to test our hypothesis, we assessed the DNA damage repair response in E47 KO mice using flow cytometry by measuring the expression level of the γ-pH2A.X. Although we found normal numbers of phenotypic HSCs under steady-state homeostasis, the γ-pH2A.X response in E47 null mice is increased respect to the E47 WT control group. This is the first evidence showing that deficiency of E47 leads to increased DNA damage response in HSCs and other early progenitors subset. Further investigations on the role of E47 in the response to DNA damage may provide novel insights into aging and exhaustion of HSCs.