A versatile tissue-rolling technique for spatial-omics analyses of the entire murine gastrointestinal tract.

Tissues are dynamic and complex biological systems composed of specialized cell types that interact with each other for proper biological function. To comprehensively characterize and understand the cell circuitry underlying biological processes within tissues, it is crucial to preserve their spatial information. Here we report a simple mounting technique to maximize the area of the tissue to be analyzed, encompassing the whole length of the murine gastrointestinal (GI) tract, from mouth to rectum.

B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing.

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity.

Interleukin-10 regulates goblet cell numbers through Notch signaling in the developing zebrafish intestine.

Cytokines are immunomodulatory proteins that orchestrate cellular networks in health and disease. Among these, interleukin (IL)-10 is critical for the establishment of intestinal homeostasis, as mutations in components of the IL-10 signaling pathway result in spontaneous colitis. Whether IL-10 plays other than immunomodulatory roles in the intestines is poorly understood.

The spatial transcriptomic landscape of the healing mouse intestine following damage.

The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing.

Levels of low-molecular-weight hyaluronan in periodontitis-treated patients and its immunostimulatory effects on CD4 T lymphocytes.

Objectives: During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic potential on T lymphocytes remain in periodontal tissues after periodontal treatment.

Materials And Methods: GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA.

Alzheimer's Disease-Like Pathology Triggered by in Wild Type Rats Is Serotype Dependent.

Periodontal disease is a disease of tooth-supporting tissues. It is a chronic disease with inflammatory nature and infectious etiology produced by a dysbiotic subgingival microbiota that colonizes the gingivodental sulcus. Among several periodontal bacteria, () highlights as a keystone pathogen.

O-Polysaccharide Plays a Major Role on the Virulence and Immunostimulatory Potential of During Periodontal Infection.

is a Gram-negative oral bacterium with high immunostimulatory and pathogenic potential involved in the onset and progression of periodontitis, a chronic disease characterized by aberrant immune responses followed by tooth-supporting bone resorption, which eventually leads to tooth loss. While several studies have provided evidence related to the virulence factors of involved in the host cell death and immune evasion, such as its most studied primate-specific virulence factor, leukotoxin, the role of specific lipopolysaccharide (LPS) domains remain poorly understood. Here, we analyzed the role of the immunodominant domain of the LPS of termed O-polysaccharide (O-PS), which differentiates the distinct bacterial serotypes based on its antigenicity.

Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis.

The alveolar bone resorption is a distinctive feature of periodontitis progression and determinant for tooth loss. Regulatory T lymphocytes (Tregs) display immuno-suppressive mechanisms and tissue repairing functions, which are critical to support periodontal health. Tregs may become unstable and dysfunctional under inflammatory conditions, which can even accelerate tissue destruction.

Overexpression of MMPs, cytokines, and RANKL/OPG in temporomandibular joint osteoarthritis and their association with joint pain, mouth opening, and bone degeneration: A preliminary report.

Objective: This study aimed to determine the expression of distinct matrix metalloproteinases, cytokines, and bone resorptive factors in temporomandibular joint osteoarthritis (TMJ-OA) patients and their association with joint pain, mouth opening, and subchondral bone degeneration.

Materials And Methods: Twelve patients affected with TMJ-OA (n = 5), disk displacement without reduction (DDWoR) (n = 3), or disk displacement with reduction (DDWR) (n = 4) were selected. Joint pain was quantified by using visual analog scale, mouth opening was quantified at the maximum pain-free aperture, and bone degeneration was quantified using joint imaging.

Induces Autophagy in Human Junctional Epithelium Keratinocytes.

The adverse environmental conditions found in the periodontium during periodontitis pathogenesis stimulate local autophagy responses, mainly due to a continuous inflammatory response against the dysbiotic subgingival microbiome. The junctional epithelium represents the main site of the initial interaction between the host and the dysbiotic biofilm. Here, we investigated the role of autophagy in junctional epithelium keratinocytes (JEKs) in response to or its purified lipopolysaccharides (LPS).

Inhibitory effect of serotype a of Aggregatibacter actinomycetemcomitans on the increased destructive potential of serotype b.

Objective: The serotype b of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) induces higher cytokine production in dendritic cells (DCs) compared with the other serotypes. However, this increased immunostimulatory potential was modified when DCs were co-infected with the other A.

Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms.

The maxillofacial skeleton is highly dynamic and requires a constant equilibrium between the bone resorption and bone formation. The field of osteoimmunology explores the interactions between bone metabolism and the immune response, providing a context to study the complex cellular and molecular networks involved in oro-maxillofacial osteolytic diseases. In this review, we present a framework for understanding the potential mechanisms underlying the immuno-pathobiology in etiologically-diverse diseases that affect the oral and maxillofacial region and share bone destruction as their common clinical outcome.

Serotype b of triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer's disease (AD), both highly prevalent pathologies among the elderly. The bacteria  (), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Here, we determined the effects of purified LPS, from serotypes a, b or c of , on primary cultures of microglia or mixed hippocampal cells.

IL-22-expressing CD4 AhR T lymphocytes are associated with RANKL-mediated alveolar bone resorption during experimental periodontitis.

Background And Objective: Over the past few years, the importance of interleukin-22 (IL-22) and T-helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL-22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis-affected patients. In addition, IL-22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro.

Multifunctional nanocarriers for the treatment of periodontitis: Immunomodulatory, antimicrobial, and regenerative strategies.

Periodontitis is an inflammatory disease, in which the host immuno-inflammatory response against the dysbiotic subgingival biofilm leads to the breakdown of periodontal tissues. Most of the available treatments seem to be effective in the short-term; nevertheless, permanent periodical controls and patient compliance compromise long-term success. Different strategies have been proposed for the modulation of the host immune response as potential therapeutic tools to take a better care of most susceptible periodontitis patients, such as drug local delivery approaches.

The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review.

This systematic review aimed to: (a) generate a descriptive synthesis of preclinical studies assessing the therapeutic potential of regulatory T lymphocytes (Tregs) to arrest periodontitis, (b) evaluate the methodological heterogeneity of the reviewed animal studies and (c) assess the risk of bias (RoB) of the included studies. The electronic search for animal studies included the MEDLINE, EMBASE, Web of Science and LILACS databases. In addition, a manual search assessed the high-ranked scientific journals in "periodontics/immunology" and the references listed in the included studies.

Immunostimulatory activity of low-molecular-weight hyaluronan on dendritic cells stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis.

Objectives: Periodontitis is a chronic inflammatory disease characterized by tooth-supporting tissue destruction, which is elicited by the host's immune response triggered against periodonto-pathogen bacteria. During periodontal tissue destruction, extracellular matrix components are metabolized and fragmented. Some extracellular matrix component-derived fragments, such as low-molecular-weight hyaluronan (LMW-HA), have potent immunogenic potential, playing a role as damage-associated molecular patterns (DAMPs) during activation of immune cells.

Alveolar bone resorption and Th1/Th17-associated immune response triggered during Aggregatibacter actinomycetemcomitans-induced experimental periodontitis are serotype-dependent.

Background: Aggregatibacter actinomycetemcomitans expresses several virulence factors that may contribute to the pathogenesis of periodontitis. Based on the antigenicity of the O-polysaccharide component of the lipopolysaccharide (LPS), different A. actinomycetemcomitans serotypes have been described.

Serotype a of Aggregatibacter actinomycetemcomitans down-regulates the increased serotype b-induced cytokine and chemokine production in dendritic cells.

Objective: In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Mixed infection with the different A. actinomycetemcomitans serotypes is frequent in periodontitis patients; accordingly, the role of this bacterial species in the pathogenesis of periodontitis may differ depending whether patients or periodontal lesions harbour one or more of the A.

Regulatory T Lymphocytes in Periodontitis: A Translational View.

Periodontitis is a chronic immuno-inflammatory disease in which the disruption of the balance between host and microbiota interactions is key to the onset and progression of the disease. The immune homeostasis associated with periodontal health requires a regulated immuno-inflammatory response, during which the presence of regulatory T cells (Tregs) is essential to ensure a controlled response that minimizes collateral tissue damage. Since Tregs modulate both innate and adaptive immunity, pathological conditions that may resolve by the acquisition of immuno-tolerance, such as periodontitis, may benefit by the use of Treg immunotherapy.

Th1/Th17/Th22 immune response and their association with joint pain, imagenological bone loss, RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: A preliminary report.

It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno-inflammatory response in the joint environment, such as IL-1β, IL-17 and IL-22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ-OA), IL-1β and IL-17 have been implicated in the inflammation and resorption of sub-chondral bone; however, the role of Th22 response in the TMJ-OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22-type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ-OA or disk displacement with reduction (DDWR) patients.

Increased levels of the T-helper 22-associated cytokine (interleukin-22) and transcription factor (aryl hydrocarbon receptor) in patients with periodontitis are associated with osteoclast resorptive activity and severity of the disease.

Background And Objective: Two new T-helper (Th) phenotypes have been recently described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study was aimed to assess whether Th9 and Th22 lymphocytes, through interleukin (IL)-9 and IL-22 production, respectively, are associated with the severity of periodontitis and bone resorption.

Material And Methods: Gingival crevicular fluid samples and biopsies were obtained from patients with moderate-to-advanced chronic periodontitis and gingivitis, and healthy controls.

Differential human Th22-lymphocyte response triggered by Aggregatibacter actinomycetemcomitans serotypes.

Objective: In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on lipopolysaccharide (LPS) antigenicity. When T lymphocytes were stimulated with these serotypes, different patterns of T-helper (Th)1 and Th17-type of immune responses were reported. Recently, two new Th phenotypes have been described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear.