Date Published: March 02, 2018
Publisher: Impact Journals
Author(s): Xin Wang, Justin Darcy, Chuan Cai, Junfei Jin, Andrzej Bartke, Deliang Cao.
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.
Ames dwarf mice possess a spontaneous Prophet of Pituitary Factor 1 (Prop1) loss-of-function mutation. The mutation of the Prop1 gene results in the lack of differentiation of endocrine cell lineages (somatotrophs, lactotrophs and thyrotrophs) in the anterior pituitary. Therefore, 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) . Particularly important is the deficiency of GH and IGF-1 signaling (collectively referred to as somatotropic signaling) , which is believed to be the principle force behind the approximately 50% increase in longevity observed in Ames dwarf mice (depending on sex and diet) . 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 . However, it is unclear how the somatotropic signaling (GH/IGF-1) defect affects the colon development and intestinal immunity in these mice.
The present study investigated the colon development and immune cells in the cLP and MLNs of Ames dwarf mice with WT mice at the same age as a control. Ames dwarf mice are GH-deficient due to a mutation in a pituitary-specific, paired-like homeodomain transcription factor gene, Prop1. The growth and maturation of dwarf mice are delayed and we assayed the immune cells at the ages of 2 months and six months old, respectively. Herein we termed the mice at 2 months as juvenile and mice at 6 months as adult.