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Intestinal immunity in hypopituitary dwarf mice: effects of age.

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 (?: 0.15% vs. 0.03% in WT mice) and monocytes (?: 7.97% vs. 5.15%) infiltrated, and antigen presenting cells CD11c+ dendritic cells (?: 1.39% vs. 0.87%), CD11b+ macrophages (?: 3.22% vs. 0.81%) and gamma delta T (?? T) cells (?: 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 (?: 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 (?: 7.7% vs.10.5%), but an increase of Th17 cells (?: 0.627% vs.0.093%). Taken together, these data suggest that somatotropic signaling deficiency influences colon development and intestinal immunity.

SUBMITTER: Wang X

PROVIDER: S-EPMC5892686 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Intestinal immunity in hypopituitary dwarf mice: effects of age.

Wang Xin X Darcy Justin J Cai Chuan C Jin Junfei J Bartke Andrzej A Cao Deliang D

Aging 20180301 3

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 pres ...[more]

PMID: 29500333

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Project description:The interactions among humans, their environment, and the trillions of microbes residing within the human intestinal tract form a tripartite relationship that is fundamental to the overall health of the host. Disruptions in the delicate balance between the intestinal microbiota and host immunity are implicated in various chronic diseases, including inflammatory bowel disease (IBD). There is no known cure for IBD; therefore, novel therapeutics targeting prevention and symptom management are of great interest. Recently, physical activity in healthy mice was shown to be protective against chemically induced colitis; however, the benefits of physical activity during or following disease onset are not known. In this study, we examine whether voluntary wheel running is protective against primary disease symptoms in a mucin 2-deficient (Muc2-/- ) lifelong model of murine colitis. We show that 6 weeks of wheel running in healthy C57BL/6 mice leads to distinct changes in fecal bacteriome, increased butyrate production, and modulation in colonic gene expression of various cytokines, suggesting an overall primed anti-inflammatory state. However, these physical activity-derived benefits are not present in Muc2-/- mice harboring a dysfunctional mucosal layer from birth, ultimately showing no improvements in clinical signs. We extrapolate from our findings that while physical activity in healthy individuals may be an important preventative measure against IBD, for those with a compromised intestinal mucosa, a commonality in IBD patients, these benefits are lost.IMPORTANCE Perturbation in the gut microbial ecosystem has been associated with various diseases, including inflammatory bowel disease. Habitual physical activity, through its ability to modulate the gut microbiome, has recently been shown to prophylactically protect against chemically induced models of murine colitis. Here, we (i) confirm previous reports that physical activity has limited but significant effects on the gut microbiome of mice and (ii) show that such changes are associated with anti-inflammatory states in the gut, such as increased production of beneficial short-chain fatty acids and lower levels of proinflammatory immune markers implicated in human colitis; however, we also show that (iii) these physical activity-derived benefits are completely lost in the absence of a healthy intestinal mucus layer, a hallmark phenotype of human colitis.

Dataset Information

Intestinal immunity in hypopituitary dwarf mice: effects of age.

Publications

Intestinal immunity in hypopituitary dwarf mice: effects of age.

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