Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs.

In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extraembryonic compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.

Thymic mimetic cells function beyond self-tolerance.

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2-7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations.

The disulfide catalyst QSOX1 maintains the colon mucosal barrier by regulating Golgi glycosyltransferases.

Mucus is made of enormous mucin glycoproteins that polymerize by disulfide crosslinking in the Golgi apparatus. QSOX1 is a catalyst of disulfide bond formation localized to the Golgi. Both QSOX1 and mucins are highly expressed in goblet cells of mucosal tissues, leading to the hypothesis that QSOX1 catalyzes disulfide-mediated mucin polymerization. We found that knockout mice lacking QSOX1 had impaired mucus barrier function due to production of defective mucus. However, an investigation on the molecular level revealed normal disulfide-mediated polymerization of mucins and related glycoproteins. Instead, we detected a drastic decrease in sialic acid in the gut mucus glycome of the QSOX1 knockout mice, leading to the discovery that QSOX1 forms regulatory disulfides in Golgi glycosyltransferases. Sialylation defects in the colon are known to cause colitis in humans. Here we show that QSOX1 redox control of sialylation is essential for maintaining mucosal function.

Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.

Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome-wide association studies and experimental animal models point at a central role of the IL-10 axis in inflammatory bowel diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10Rα) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1-expressing macrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages and resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning agent in the colon and define intestinal CX3CR1(hi) macrophages as a decisive factor that determines gut health or inflammation.

Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys.

Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify "p10" and "p15" as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that many mammal chapparvoviruses are likely to be nephrotropic.

Neutralization of pro-inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis.

Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll-like receptor 2(TLR2) dimerization by a TLR2 transmembrane peptide (TLR2-p) ameliorated DSS-induced colitis by interfering specifically with the activation of Ly6C(+) monocytes without affecting their recruitment to the colon. We report that TLR2-p directly interacts with TLR2 within the membrane, leading to inhibition of TLR2-TLR6/1 assembly induced by natural ligands. This was associated with decreased levels of extracellular signal-regulated kinases (ERK) signaling and reduced secretion of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-23, IL-12, and IL-1ß. Altogether, our study provides insights into the essential role of TLR2 dimerization in the activation of pathogenic pro-inflammatory Ly6C(hi) monocytes and suggests that inhibition of this aggregation by TLR2-p might have therapeutic potential in the treatment of acute gut inflammation.

Aberrant Mesenteric Migration of Spirocerca lupi Larvae Causing Necrotizing Eosinophilic Arteritis, Thrombosis, and Intestinal Infarction in Dogs.

This report presents a novel canine condition in 32 dogs in which aberrant migration of Spirocerca lupi larvae through mesenteric arteries, instead of gastric arteries, led to small or large intestinal infarction. This form of spirocercosis was first recognized in Israel in 2013 and is currently ongoing. Typical clinical signs were anorexia and weakness of 3 to 4 days and, less frequently, vomiting and diarrhea, followed by collapse, bloody diarrhea, and severe vomiting. Exploratory laparotomy showed 1 or more infarcted and often perforated intestinal segments in all cases. Microscopically, there was intestinal mucosal to transmural coagulative necrosis and mesenteric multifocal necrotizing eosinophilic arteritis, thrombosis, hemorrhage, and early fibroplasia. Third-stage S. lupi larvae were identified by morphologic features in 9 of 32 (28%) cases, and the species was confirmed by polymerase chain reaction in 4 cases. Nearly 50% of the dogs had been receiving prophylactic therapy, which did not prevent this form of spirocercosis.

Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration.

Following myonecrosis, muscle satellite cells proliferate, differentiate and fuse, creating new myofibers. The Runx1 transcription factor is not expressed in naïve developing muscle or in adult muscle tissue. However, it is highly expressed in muscles exposed to myopathic damage yet, the role of Runx1 in muscle regeneration is completely unknown. Our study of Runx1 function in the muscle's response to myonecrosis reveals that this transcription factor is activated and cooperates with the MyoD and AP-1/c-Jun transcription factors to drive the transcription program of muscle regeneration. Mice lacking dystrophin and muscle Runx1 (mdx-/Runx1f/f), exhibit impaired muscle regeneration leading to age-dependent muscle waste, gradual decrease in motor capabilities and a shortened lifespan. Runx1-deficient primary myoblasts are arrested at cell cycle G1 and consequently differentiate. Such premature differentiation disrupts the myoblasts' normal proliferation/differentiation balance, reduces the number and size of regenerating myofibers and impairs muscle regeneration. Our combined Runx1-dependent gene expression, ChIP-seq, ATAC-seq and histone H3K4me1/H3K27ac modification analyses revealed a subset of Runx1-regulated genes that are co-occupied by MyoD and c-Jun in mdx-/Runx1f/f muscle. The data provide unique insights into the transcriptional program driving muscle regeneration and implicate Runx1 as an important participant in the pathology of muscle wasting diseases.

Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome.

Dendritic cells are critically involved in the promotion and regulation of T cell responses. Here, we report a mouse strain that lacks conventional CD11c(hi) dendritic cells (cDCs) because of constitutive cell-type specific expression of a suicide gene. As expected, cDC-less mice failed to mount effective T cell responses resulting in impaired viral clearance. In contrast, neither thymic negative selection nor T regulatory cell generation or T cell homeostasis were markedly affected. Unexpectedly, cDC-less mice developed a progressive myeloproliferative disorder characterized by prominent extramedullary hematopoiesis and increased serum amounts of the cytokine Flt3 ligand. Our data identify a critical role of cDCs in the control of steady-state hematopoiesis, revealing a feedback loop that links peripheral cDCs to myelogenesis through soluble growth factors, such as Flt3 ligand.

Polioencephalomyelopathy in a mixed breed dog resembling Leigh's disease.

A 14-month-old mixed-breed dog was presented with acute onset of exercise intolerance that quickly progressed to quadriparesis. Gross and microscopic autopsy findings indicated a type of degenerative polioencephalomyelopathy resembling subacute necrotizing encephalomyelopathy in dogs or Leigh's disease in humans. This syndrome has previously been reported only in purebred dogs.

Polioencéphalomyélopathie chez un chien de race croisée ressemblant au syndrome de Leigh. Un chien de race croisée âgé de 14 mois a été présenté avec l'apparition aiguë d'intolérance à l'exercice qui a rapidement progressé à la quadriparésie. Suite à la nécropsie, les constatations macroscopiques et microscopique ont indiqué un type de polioencéphalomyélopathie dégénérative ressemblant à l'encéphalomyélopathie nécrosante subaiguë chez les chiens ou au syndrome de Leigh chez les humains. Ce syndrome avait été signalé précédemment seulement chez les chiens de race pure.(Traduit par Isabelle Vallières).

Competitive fungal commensalism mitigates candidiasis pathology.

The mycobiota are a critical part of the gut microbiome, but host-fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans-mediated diseases.

Man made disease: clinical manifestations of low phenylalanine levels in an inadequately treated phenylketonuria patient and mouse study.

INTRODUCTION: Phenylalanine (Phe) deficiency and its clinical manifestations have been previously described mostly as sporadic case reports dating back to the 1960's and 1970's. In these reports, low plasma Phe levels were associated with listlessness, eczematous eruptions and failure to gain weight, most often in infants in their first year of life. CASE REPORT: Herein we describe a 9 month old female patient with known phenylketonuria, who presented with an unusual constellation of symptoms, including severe erythema and desquamation, alopecia, keratomalacia, corneal perforation, failure to thrive and prolonged diarrhea. The diagnostic possibilities of acrodermatitis enteropathica and vitamin deficiencies were ruled out, and further investigation into her medical history led to the conclusion that during the weeks preceding the hospitalization, the patient's diet consisted of the phenylalanine-free medical formula alone, without the addition of a standard infant formula or food as recommended. Subsequently, dietary control of the blood phenylalanine levels brought swift and marked resolution of the dermatological lesions, with renewal of hair growth. OBJECTIVE: Following this experience, and due to the relative paucity of data regarding the clinical manifestations of low serum phenylalanine levels in humans and their putative pathogenetic mechanisms, we sought to further investigate the effects of a phenylalanine-free diet in a mouse study. MATERIALS AND METHODS: For this purpose, twenty mice were randomly allocated to receive either a phenylalanine-deficient diet (n=10) or a normal diet (n=10). Weight was measured weekly, and laboratory tests were obtained including complete blood count, electrolyte studies, and phenylalanine and tyrosine levels. Finally, necropsies and histopathological examinations of different tissues were performed in selected mice, either early after diet initiation, late after diet initiation or following re-introduction of normal diets. The study was then repeated in additional two groups of mice, for a period of up to thirteen weeks, with a total of 63 mice. RESULTS: Gross lesions noted on necropsy in the Phe-deficient mice included scruffy coat, tendency toward weight loss, a reduction in thymic mass, and most notably severe gastric dilation, all of which were not seen in the controls. Histologic findings included thymic depletion, hepatocellular vacuolation, and exocrine pancreatic atrophy. No histopathological lesions were evident in the brain, nor were significant lesions in the eyes. CONCLUSIONS: Diagnosis of the iatrogenic condition of phenylalanine deficiency, which manifests in gastrointestinal, dermatological and ocular findings, requires a high index of suspicion. Mice fed a phenylalanine-deficient diet display to some extent similar organ involvement, although no eye abnormalities were evident.

High-sensitivity deuterium metabolic MRI differentiates acute pancreatitis from pancreatic cancers in murine models.

Deuterium metabolic imaging (DMI) is a promising tool for investigating a tumor's biology, and eventually contribute in cancer diagnosis and prognosis. In DMI, [6,6'-2H2]-glucose is taken up and metabolized by different tissues, resulting in the formation of HDO but also in an enhanced formation of [3,3'-2H2]-lactate at the tumor site as a result of the Warburg effect. Recent studies have shown DMI's suitability to highlight pancreatic cancer in murine models by [3,3'-2H2]-lactate formation; an important question is whether DMI can also differentiate between these tumors and pancreatitis. This differentiation is critical, as these two diseases are hard to distinguish today radiologically, but have very different prognoses requiring distinctive treatments. Recent studies have shown the limitations that hyperpolarized MRI faces when trying to distinguish these pancreatic diseases by monitoring the [1-13C1]-pyruvate→[1-13C1]-lactate conversion. In this work, we explore DMI's capability to achieve such differentiation. Initial tests used a multi-echo (ME) SSFP sequence, to identify any metabolic differences between tumor and acute pancreatitis models that had been previously elicited very similar [1-13C1]-pyruvate→[1-13C1]-lactate conversion rates. Although ME-SSFP provides approximately 5 times greater signal-to-noise ratio (SNR) than the standard chemical shift imaging (CSI) experiment used in DMI, no lactate signal was observed in the pancreatitis model. To enhance lactate sensitivity further, we developed a new, weighted-average, CSI-SSFP approach for DMI. Weighted-average CSI-SSFP improved DMI's SNR by another factor of 4 over ME-SSFP-a sensitivity enhancement that sufficed to evidence natural abundance 2H fat in abdominal images, something that had escaped the previous approaches even at ultrahigh (15.2 T) MRI fields. Despite these efforts to enhance DMI's sensitivity, no lactate signal could be detected in acute pancreatitis models (n = 10; [3,3'-2H2]-lactate limit of detection < 100 µM; 15.2 T). This leads to the conclusion that pancreatic tumors and acute pancreatitis may be clearly distinguished by DMI, based on their different abilities to generate deuterated lactate.

Encephalopathy caused by ablation of very long acyl chain ceramide synthesis may be largely due to reduced galactosylceramide levels.

Sphingolipids (SLs) act as signaling molecules and as structural components in both neuronal cells and myelin. We now characterize the biochemical, histological, and behavioral abnormalities in the brain of a mouse lacking very long acyl (C22-C24) chain SLs. This mouse, which is defective in the ability to synthesize C22-C24-SLs due to ablation of ceramide synthase 2, has reduced levels of galactosylceramide (GalCer), a major component of myelin, and in particular reduced levels of non-hydroxy-C22-C24-GalCer and 2-hydroxy-C22-C24- GalCer. Noteworthy brain lesions develop with a time course consistent with a vital role for C22-C24-GalCer in myelin stability. Myelin degeneration and detachment was observed as was abnormal motor behavior originating from a subcortical region. Additional abnormalities included bilateral and symmetrical vacuolization and gliosis in specific brain areas, which corresponded to some extent to the pattern of ceramide synthase 2 expression, with astrogliosis considerably more pronounced than microglial activation. Unexpectedly, unidentified storage materials were detected in lysosomes of astrocytes, reminiscent of the accumulation that occurs in lysosomal storage disorders. Together, our data demonstrate a key role in the brain for SLs containing very long acyl chains and in particular GalCer with a reduction in their levels leading to distinctive morphological abnormalities in defined brain regions.

Nuclear survivin expression as a potentially useful tool for the diagnosis of canine cutaneous sebaceous lesions.

BACKGROUND: Sebaceous glands are specialized cutaneous adnexal glands, which work under constant hormonal control to produce sebum. They can give rise to several proliferative lesions, such as hamartoma, hyperplasia and neoplasms (adenoma, epithelioma and carcinoma). Their nomenclature is currently confusing, both in veterinary and in human medicine, owing to the difficulty of differentiating between some of these lesions. METHODS: The present study used immunohistochemistry to determine the expression levels and patterns of survivin and Ki67 in five samples of normal canine skin and 44 cases of canine cutaneous lesions with sebaceous differentiation (10 hamartomas, nine hyperplasia, eight adenomas, eight epitheliomas and nine carcinomas). RESULTS: In normal glands, survivin, as well as Ki67, was expressed in scattered reserve cells. In hamartomas, survivin was more highly expressed than in normal skin, indicating a possible role of this molecule in the pathogenesis of these congenital lesions. In tumours, a moderate or high level of survivin and Ki67 expression (more than two and four and more than two positive cells, respectively) were significantly correlated with a malignant histotype, infiltrative growth and a moderate or high number of mitoses (more than two). CONCLUSIONS AND CLINICAL IMPORTANCE: The level of survivin expression increased with increasing malignancy, designating survivin as a new diagnostic marker in the assessment of malignancy of sebaceous tumours.

Spontaneous intradural disc herniation with focal distension of the subarachnoid space in a dog.

Myelo-computed tomography of a paraparetic 14-year-old dog revealed subarachnoid distension with an intradural filling defect above the T13-L1 disc space. T12-L1 hemilaminectomy followed by durotomy allowed removal of a large piece of degenerated disc material that compressed the spinal parenchyma. Full return to function was achieved 10 days post-surgery. The distension was likely secondary to the intradural herniation, and is a rare and distinct finding.

Hernie discale intra-durale spontanée avec distension focale de l'espace sous-arachnoïdien chez un chien. Une myélo-tomographie par ordinateur d'un chien paraparétique âgé de 14 ans a révélé une distension sous-arachnoïdienne avec un défaut de remplissage intradural au-dessus de l'espace du disque T13­L1. Une hémilaminectomie de T12­L1 suivie d'une durotomie ont permis l'enlèvement d'un grand morceau de matériel dégénéré du disque qui comprimait le parenchyme rachidien. Un retour complet à la fonction a été obtenu 10 jours après la chirurgie. La distension était probablement secondaire à l'hernie intradurale et représente une constatation rare et distincte.(Traduit par Isabelle Vallières).

Evaluation of a treatment protocol in dogs with intraspinal spirocercosis.

OBJECTIVE: To evaluate the efficiency and safety of a doramectin-based treatment protocol in dogs affected by intraspinal spirocercosis (Spirocerca lupi). ANIMALS: Client-owned dogs that were admitted to a veterinary hospital during 2021 to 2022 with acute onset of neurological signs and diagnosed with intraspinal spirocercosis. All dogs underwent complete neurological evaluation, CSF analysis, PCR confirmation of CNS S lupi infection, and follow-up evaluation of at least 6 months. PROCEDURES: Upon diagnosis, dogs were treated with doramectin at a dose of 400 µg/kg, SC, q 24 h for 3 consecutive days, followed by the same dose once a week for 6 weeks. Prednisone was administered at a dose of 1 mg/kg, PO, q 24 h and tapered every 3 days. Antimicrobial clindamycin was administered at a dose of 12.5 mg/kg, PO, q 12 h for 7 days to reduce the risk of secondary spinal cord infection. Short- and long-term outcomes (1 week to 56 months) were recorded. RESULTS: 8 dogs fulfilled the inclusion criteria, 7 of which presented with neurological deficits and 1 with cervical pain. Initiation of treatment was associated with stopping the deterioration in 7 of 8 dogs. Seven dogs improved and 6 recovered ambulation. One dog was euthanized due to lack of improvement. Six of the recovered dogs were still ataxic on the last follow-up examination at 6 to 56 months. No adverse effects of the drug were noted. CLINICAL RELEVANCE: Frequent administration of doramectin was found to be safe and effective in preventing neurological deterioration in dogs with intraspinal spirocercosis.

A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy.

We have generated a mouse that cannot synthesize very long acyl chain (C22-C24) ceramides (Pewzner-Jung, Y., Park, H., Laviad, E. L., Silva, L. C., Lahiri, S., Stiban, J., Erez-Roman, R., Brugger, B., Sachsenheimer, T., Wieland, F. T., Prieto, M., Merrill, A. H., and Futerman, A. H. (2010) J. Biol. Chem. 285, 10902-10910) due to ablation of ceramide synthase 2 (CerS2). As a result, significant changes were observed in the sphingolipid profile of livers from these mice, including elevated C16-ceramide and sphinganine levels. We now examine the functional consequences of these changes. CerS2 null mice develop severe nonzonal hepatopathy from about 30 days of age, the age at which CerS2 expression peaks in wild type mice, and display increased rates of hepatocyte apoptosis and proliferation. In older mice there is extensive and pronounced hepatocellular anisocytosis with widespread formation of nodules of regenerative hepatocellular hyperplasia. Progressive hepatomegaly and noninvasive hepatocellular carcinoma are also seen from approximately 10 months of age. Even though CerS2 is found at equally high mRNA levels in kidney and liver, there are no changes in renal function and no pathological changes in the kidney. High throughput analysis of RNA expression in liver revealed up-regulation of genes associated with cell cycle regulation, protein transport, cell-cell interactions and apoptosis, and down-regulation of genes associated with intermediary metabolism, such as lipid and steroid metabolism, adipocyte signaling, and amino acid metabolism. In addition, levels of the cell cycle regulator, the cyclin dependent-kinase inhibitor p21(WAF1/CIP1), were highly elevated, which occurs by at least two mechanisms, one of which may involve p53. We propose a functional rationale for the synthesis of sphingolipids with very long acyl chains in liver homeostasis and in cell physiology.

Beneficial effect of glatiramer acetate treatment on syndecan-1 expression in dextran sodium sulfate colitis.

Syndecan-1, the most abundant heparan sulfate proteoglycan in the gastrointestinal tract, is reduced in the regenerative epithelium in inflammatory bowel disease (IBD). This study explored the effects of the immunomodulator glatiramer acetate (GA; Copaxone) treatment on syndecan-1 expression in dextran sodium sulfate (DSS)-induced colitis. Acute and chronic colitis was induced in C57BL/6 mice by 2 and 1.5% DSS in tap water, respectively. GA was applied subcutaneously, 2 mg per mouse per day, starting on the day of DSS induction until the mice were sacrificed. Syndecan-1 expression was assessed by immunohistochemistry. The effect of adoptive transfer of GA-specific T cells as an organ-specific therapy also was evaluated. Syndecan-1 expression was significantly lower in both colitis groups compared with that in naive mice (p < 0.0001). GA attenuated clinical scores and pathological manifestations of colitis and led to the reinstatement of normal levels of syndecan-1. After adoptive transfer, GA-specific cells homed to the surface epithelium of the distal colon, accompanied by the augmentation of syndecan-1 staining in their vicinity. We concluded that syndecan-1 expression is reduced in DSS-induced colitis and could be a potential prognostic factor in IBD. Treatment with GA exerts not only an anti-inflammatory effect but also a possible beneficial effect in stabilizing the intestinal epithelium barrier and tissue repair in DSS colitis. GA may be applied as a novel drug for IBD, shifting treatment from immunosuppression toward immunomodulation.