Nab2 maintains thymus cellularity with aging and stress.

Area of Science:

• Immunology
• Molecular Genetics
• Developmental Biology

Background:

• Thymic cellularity is influenced by age and stress, but molecular regulators are poorly understood.
• Immediate early genes (Egrs) and their co-regulator Nab2 are involved in immune function and stress responses.
• Nab2's role in the thymus, unlike its known role in peripheral T-cell activation, remains uninvestigated.

Purpose of the Study:

• To investigate the role of Nab2 in the thymus.
• To determine the effect of Nab2 deficiency on thymic cellularity in response to aging and stress.
• To explore potential sex-dependent effects of Nab2 deficiency.

Main Methods:

• Utilized Nab2-deficient (KO) and wildtype (WT) mice for comparative analysis.
• Assessed thymus size and thymocyte numbers in relation to age and sex.
• Investigated the impact of restraint stress on thymic cellularity and thymocyte subset populations.

Main Results:

• Male Nab2KO mice exhibited reduced thymus size and thymocyte numbers compared to WT males, with accelerated loss over time.
• Female Nab2KO mice did not show significant differences in thymocyte numbers or age-related loss compared to WT females.
• Restraint stress significantly decreased thymic cellularity in both Nab2KO and WT mice, but altered thymocyte subset proportions (DP, CD4SP, CD8SP) only in Nab2KO males.

Conclusions:

• Nab2 is essential for maintaining thymocyte numbers in male mice throughout aging.
• Nab2 plays a critical role in the thymic response to stress, particularly in males.
• The findings highlight a sex-dependent requirement for Nab2 in thymic regulation.