Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

Rodriguez-Palacios, Alexander; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott J.; Katz, Jeffry; Wei, Xin; Pizarro, Theresa T.; Cominelli, Fabio

doi:10.1038/ncomms8577

Cited by 64 publications

(111 citation statements)

References 69 publications

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“…A complex microbial community was insufficient for generating a robust population of Th17 cells in the gut of SPF mice lacking SFB (9, 10) and gnotobiotic mice colonized long term with human fecal contents (42). Although SFB has been detected in multiple vertebrate species (43), there exists only sparse evidence of a related microbe colonizing humans (43)(44)(45)(46). A recent study showed that a consortium of 20 symbionts from the feces of an IBD patient could induce Th17 cells in mice but failed to identify the active microbes in healthy people (11).…”

Section: Discussionmentioning

confidence: 99%

“…These pathways could potentially regulate the activity of mechanosensitive integrins and cytokines (e.g., TGF-β) relevant to Th17 cell differentiation and trafficking. Interestingly, DNA from SFB-like microbes was recently enriched in the gut of human IBD patients, associated with cavernous fistulous tracts running between muscle bundles (46). The enrichment for muscle-related pathways in whole-tissue SI-LP preparations from mice colonized with B. adolescentis hints at a more general relationship between Th17-inducing microbes and intestinal muscle tissue.…”

Section: Discussionmentioning

confidence: 99%

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Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Tan

Sefik

Geva‐Zatorsky

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

361

287

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Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Tan

Sefik

Geva‐Zatorsky

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

361

287

View full text Add to dashboard Cite

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“…Three-dimensional stereomicroscopy assessment and pattern profiling serve to map and quantify the intestinal health in mice and to determine the extent of mucosal involvement that occurs with acute and chronic inflammation (18). To analyze the variable patterns of stereomicroscopic abnormalities, stereomicroscopy photographs were analyzed using ImageJ public domain software (imagej.nih.gov/ij/).…”

Section: Methodsmentioning

confidence: 99%

Protective Role for TWEAK/Fn14 in Regulating Acute Intestinal Inflammation and Colitis-Associated Tumorigenesis

et al. 2016

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Inflammatory bowel disease causes chronic, relapsing intestinal inflammation that can lead to the development of colorectal cancer. Members of the TNF superfamily are key regulators of intestinal inflammation. In particular, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are involved in normal and pathologic intestinal tissue remodeling. In this study, we show that the TWEAK/Fn14 signaling complex plays a protective role during the acute stage of intestinal inflammation and contributes to the prevention of colitis-associated cancer during chronic inflammation through its pro-apoptotic effects. Colitis was in Fn14-/- and Fn14+/+ wild type littermates by administering 3% dextran sodium sulfate (DSS) for 7 days followed by 2 weeks recovery; azoxymethane (AOM) administration followed by 2 cycles of DSS/recovery was used to induce tumors. Reciprocal bone marrow chimeric mice were generated to compare hematopoietic and non-hematopoietic-specific effector tissues. Fn14-/- mice had enhanced susceptibility to colitis compared to Fn14+/+ controls as assessed by endoscopic and histological inflammatory scores, daily weight loss, and mortality rates during recovery after DSS administration. Bone marrow transfer experiments showed that both hematopoietic and non-hematopoietic components are involved in protection against colitis. Tumor lesions were found in the colons of most Fn14-/- mice, but not Fn14+/+ controls. AOM/DSS administration enhanced susceptibility to tumorigenesis in Fn14-/- mice. Overall, these findings show that Fn14 plays a protective role during the acute stages of intestinal inflammation, and its absence promotes the development of colitis-associated cancer.

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“… 19 Early alterations in epithelial architecture and defective barrier function are present by 3 weeks of age, preceding the onset of overt ileitis, and include increased numbers of secretory Paneth, goblet, and intermediate cells, with a simultaneous reduction in absorptive enterocytes. This trend increases at sites of active inflammation as the animals age and as the disease becomes more severe 20, 21.…”

Section: Mouse Models Of Cd-like Ileitismentioning

confidence: 99%

Uncovering Pathogenic Mechanisms of Inflammatory Bowel Disease Using Mouse Models of Crohn’s Disease–Like Ileitis: What is the Right Model?

Cominelli

Arseneau

Rodriguez-Palacios

et al. 2017

Cellular and Molecular Gastroenterology and Hepatology

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Crohn’s disease and ulcerative colitis, together known as inflammatory bowel disease, are debilitating chronic disorders of unknown cause and cure. Our evolving understanding of these pathologies is enhanced greatly by the use of animal models of intestinal inflammation that allow in vivo mechanistic studies, preclinical evaluation of new therapies, and investigation into the causative factors that underlie disease pathogenesis. Several animal models, most commonly generated in mice, exist for the study of colitis. The appropriateness of their use often can be determined by their mode of generation (ie, chemical induction, T-cell transfer, targeted genetic manipulation, spontaneously occurring, and so forth), the type of investigation (mechanistic studies, pathogenic experiments, preclinical evaluations, and so forth), and the type of inflammation that occurs in the model (acute vs chronic colitis, tissue injury/repair, and so forth). Although most murine models of inflammatory bowel disease develop inflammation in the colon, Crohn’s disease most commonly occurs in the terminal ileum, where a very limited number of mouse models manifest disease. This review discusses appropriate experimental applications for different mouse models of colitis, and highlights the particular utility of 2 highly relevant models of Crohn’s-like ileitis—the spontaneous SAMP1/YitFc inbred mouse strain and the genetically engineered TnfΔAU-rich element/+ mouse model of tumor necrosis factor overexpression, both of which bear strong resemblance to the human condition. Similar to patients with Crohn’s disease, SAMP1/YitFc ileitis develops spontaneously, without chemical, genetic, or immunologic manipulation, making this model particularly relevant for studies aimed at identifying the primary defect underlying the occurrence of Crohn’s ileitis, as well as preclinical testing of novel treatment modalities.

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Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

Cited by 64 publications

References 69 publications

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Protective Role for TWEAK/Fn14 in Regulating Acute Intestinal Inflammation and Colitis-Associated Tumorigenesis

Uncovering Pathogenic Mechanisms of Inflammatory Bowel Disease Using Mouse Models of Crohn’s Disease–Like Ileitis: What is the Right Model?

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