TY - JOUR
T1 - Nab2 maintains thymus cellularity with aging and stress
AU - Hastings, K. Taraszka
AU - Elizalde, Diana
AU - Muppana, Leela
AU - Levine, Sarah
AU - Kamel, Christy M.
AU - Ingram, Wendy M.
AU - Kirkpatrick, Jennifer T.
AU - Hu, Chengcheng
AU - Rausch, Matthew P.
AU - Gallitano, Amelia L.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation. However, a role for Nab2 in the thymus has not been reported. Using Nab2-deficient (KO) mice we found that male Nab2KO mice have reduced thymus size and decreased numbers of thymocytes, compared with age-matched wildtype (WT) mice. Furthermore, the number of thymocytes in Nab2KO males decreases more rapidly with age. This effect is sex-dependent as female Nab2KO mice show neither reduced thymocyte numbers nor accelerated thymocyte loss with age, compared to female WT littermates. Since stress induces expression of Nab2 and the Egrs, we examined whether loss of Nab2 alters stress-induced decrease in thymic cellularity. Restraint stress induced a significant decrease in thymic cellularity in Nab2KO and WT mice, with significant changes in the thymocyte subset populations only in the Nab2KO mice. Stress reduced the percentage of DP cells by half and increased the percentage of CD4SP and CD8SP cells by roughly three-fold in Nab2KO mice. These findings indicate a requirement for Nab2 in maintaining thymocyte number in male mice with age and in response to stress.
AB - Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation. However, a role for Nab2 in the thymus has not been reported. Using Nab2-deficient (KO) mice we found that male Nab2KO mice have reduced thymus size and decreased numbers of thymocytes, compared with age-matched wildtype (WT) mice. Furthermore, the number of thymocytes in Nab2KO males decreases more rapidly with age. This effect is sex-dependent as female Nab2KO mice show neither reduced thymocyte numbers nor accelerated thymocyte loss with age, compared to female WT littermates. Since stress induces expression of Nab2 and the Egrs, we examined whether loss of Nab2 alters stress-induced decrease in thymic cellularity. Restraint stress induced a significant decrease in thymic cellularity in Nab2KO and WT mice, with significant changes in the thymocyte subset populations only in the Nab2KO mice. Stress reduced the percentage of DP cells by half and increased the percentage of CD4SP and CD8SP cells by roughly three-fold in Nab2KO mice. These findings indicate a requirement for Nab2 in maintaining thymocyte number in male mice with age and in response to stress.
KW - Aging
KW - Early growth response gene
KW - Immediate early gene
KW - NGFI-A binding protein
KW - Stress
KW - Thymus
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U2 - 10.1016/j.molimm.2017.02.019
DO - 10.1016/j.molimm.2017.02.019
M3 - Article
C2 - 28282643
AN - SCOPUS:85014713885
SN - 0161-5890
VL - 85
SP - 185
EP - 195
JO - Molecular Immunology
JF - Molecular Immunology
ER -