Abstract
Hypopituitary dwarf mice demonstrate advantages of longevity, but little is known of their colon development and intestinal immunity. Herein we found that Ames dwarf mice have shorter colon and colonic crypts, but larger ratio of mesenteric lymph nodes (MLNs) over body weight than age-matched wild type (WT) mice. In the colonic lamina propria (cLP) of juvenile Ames mice, more inflammatory neutrophils (Ā: 0.15% vs. 0.03% in WT mice) and monocytes (Ā: 7.97% vs. 5.15%) infiltrated, and antigen presenting cells CD11c+ dendritic cells (Ā: 1.39% vs. 0.87%), CD11b+ macrophages (Ā: 3.22% vs. 0.81%) and gamma delta T (γδ T) cells (Ā: 5.56% vs. 1.35%) were increased. In adult Ames dwarf mice, adaptive immune cells, such as IL-17 producing CD4+ T helper (Th17) cells (Ā: 8.3% vs. 4.7%) were augmented. In the MLNs of Ames dwarf mice, the antigen presenting and adaptive immune cells also altered when compared to WT mice, such as a decrease of T-regulatory (Treg) cells in juvenile Ames mice (Ā: 7.7% vs.10.5%), but an increase of Th17 cells (Ā: 0.627% vs.0.093%). Taken together, these data suggest that somatotropic signaling deficiency influences colon development and intestinal immunity.
Highlights
Ames dwarf mice possess a spontaneous Prophet of Pituitary Factor 1 (Prop1) loss-of-function mutation
Juvenile and adult Ames dwarf mice are smaller in body weight and body length than age-matched wild type (WT) mice (Figure 1A), which is consistent with literature report [23]
The results showed that the mean percentage of CD11b+ macrophages (Ā: 3.22 vs. 0.81), CD11c+ distal colons (DC) (Ā: 1.39 vs. 0.78) and γδ T cells (Ā: 5.56 vs. 1.35), was www.aging‐us.com markedly increased in juvenile dwarf mice when compared to WT counterparts (Figure 4A-C), but in adult dwarf mice only DCs (Ā: 0.864 vs. 0.689) were slightly increased (Figure 4B)
Summary
Ames dwarf mice possess a spontaneous Prophet of Pituitary Factor 1 (Prop1) loss-of-function mutation. Ames dwarf mice are deficient in growth hormone (GH) and insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), the thyroid hormones (THs), and prolactin (PRL) [1]. Mechanisms that are responsible for the longevity of Ames dwarf mice may include improved antioxidant defense, enhanced insulin sensitivity and reduced insulin levels, reduced inflammation and cell senescence, and greater stress resistance [4]. It is unclear how the somatotropic signaling (GH/IGF-1) defect affects the colon development and intestinal immunity in these mice
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