Technical pitfalls when collecting, cryopreserving, thawing, and stimulating human T-cells.

The collection, cryopreservation, thawing, and culture of peripheral blood mononuclear cells (PBMCs) can profoundly influence T cell viability and immunogenicity. Gold-standard PBMC processing protocols have been developed by the Office of HIV/AIDS Network Coordination (HANC); however, these protocols are not universally observed. Herein, we have explored the current literature assessing how technical variation during PBMC processing can influence cellular viability and T cell immunogenicity, noting inconsistent findings between many of these studies. Amid the mounting concerns over scientific replicability, there is growing acknowledgement that improved methodological rigour and transparent reporting is required to facilitate independent reproducibility. This review highlights that in human T cell studies, this entails adopting stringent standardised operating procedures (SOPs) for PBMC processing. We specifically propose the use of HANC's Cross-Network PBMC Processing SOP, when collecting and cryopreserving PBMCs, and the HANC member network International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) PBMC Thawing SOP when thawing PBMCs. These stringent and detailed protocols include comprehensive reporting procedures to document unavoidable technical variations, such as delayed processing times. Additionally, we make further standardisation and reporting recommendations to minimise and document variability during this critical experimental period. This review provides a detailed overview of the challenges inherent to a procedure often considered routine, highlighting the importance of carefully considering each aspect of SOPs for PBMC collection, cryopreservation, thawing, and culture to ensure accurate interpretation and comparison between studies.

Effect of Bergenin on Human Gingival Fibroblast Response on Zirconia Implant Surfaces: An In Vitro Study.

The poor quality of life associated with the loss of teeth can be improved by the placing of dental implants. However, successful implantation relies on integration with soft tissues or peri-implant inflammatory disease that can lead to the loss of the implant. Pharmacological agents, such as antibiotics and antiseptics, can be used as adjunct therapies to facilitate osseointegration; however, they can have a detrimental effect on cells, and resistance is an issue. Alternative treatments are needed. Hence, this study aimed to examine the safety profile of bergenin (at 2.5 µM and 5 µM), a traditional medicine, towards human gingival fibroblasts cultured on acid-etched zirconia implant surfaces. Cellular responses were analysed using SEM, resazurin assay, and scratch wound healing assay. Qualitative assessment was conducted for morphology (day 1) and attachment (early and delayed), and quantitative evaluation for proliferation (day 1, 3, 5 and 7), and migration (0 h, 6 h and 24 h). The concentrations of bergenin at 2.5 µM and 5 µM did not demonstrate a statistically significant effect with regard to any of the cellular responses (p > 0.05) tested. In conclusion, bergenin is non-cytotoxic and is potentially safe to be used as a local pharmacological agent for the management of peri-implant inflammatory diseases.

Bone Tissue Engineering Scaffolds: Function of Multi-Material Hierarchically Structured Scaffolds.

Bone tissue engineering (BTE) is a topic of interest for the last decade, and advances in materials, processing techniques, and the understanding of bone healing pathways have opened new avenues of research. The dual responsibility of BTE scaffolds in providing load-bearing capability and interaction with the local extracellular matrix to promote bone healing is a challenge in synthetic scaffolds. This article describes the usage and processing of multi-materials and hierarchical structures to mimic the structure of natural bone tissues to function as bioactive and load-bearing synthetic scaffolds. The first part of this literature review describes the physiology of bone healing responses and the interactions at different stages of bone repair. The following section reviews the available literature on biomaterials used for BTE scaffolds followed by some multi-material approaches. The next section discusses the impact of the scaffold's structural features on bone healing and the necessity of a hierarchical distribution in the scaffold structure. Finally, the last section of this review highlights the emerging trends in BTE scaffold developments that can inspire new tissue engineering strategies and truly develop the next generation of synthetic scaffolds.

Impact of COVID-19 on Patients' Attitudes and Perceptions of Dental Health Services: A Questionnaire Based Study in an Australian University Dental Clinic.

COVID-19, the global pandemic, has significantly interrupted the provision of oral health care to many individuals. This study aims to evaluate patients' attitudes to and perceptions of dental visits in the COVID-19 pandemic and assess if socio-economic status influences their perception of risk associated with dental visits. Patients attending the dental clinic were invited to participate in this study by completing a questionnaire administered in August 2021. Composite indicators for access, attitude, perception and socio-economic status were created based on subsets of questions. A total of 247 completed questionnaires were obtained. Analysis was performed with the perception, attitude and access indicators against the socio-economic status indicator. This study found that there is a statistically significant difference between socio-economic groups and their attitudes and perceptions around dental health care services in the current COVID-19 pandemic. Individuals from lower socio-economic status groups were less influenced by the pandemic. Participants from higher socio-economic status groups were found to be more cautious around COVID-19 and its risks.

Droplet Distribution in a University Dental Clinic Setting: The Importance of High-Volume Evacuation.

The purpose of this study is to compare droplet distribution during a piezoelectric ultrasonic debridement procedure using either high-volume or slow-volume evacuation. Droplet distribution during a crown preparation with slow-volume evacuation is also examined. Fluorescein dye is added to the water reservoir and the procedures are performed by a single operator for 15 min on a dental manikin with artificial upper and lower teeth. Placement of filter paper squares (10 cm × 10 cm) in radiating lines away from the oral cavity of the dental manikin allows for visualization of droplet dispersion. Results show minimal difference in the spread of the droplets between the two evacuators during the debridement procedure; however, the slow-volume evacuator produces a higher concentration of droplets than the high-volume evacuator. An even higher concentration of droplets in the vicinity of the dental chair is observed during the crown preparation procedure. This study recommends the use of a high-volume evacuator where possible during professional debridement and crown preparation to reduce contamination around the dental chair from potentially pathogenic microorganisms.

Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.    Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training. What is Known: • Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits. • Some evidence suggests that this modulation can persist post-prophylaxis. What is New: • We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia. • We also observed limited persistence of the probiotic species post-discharge.

To Probiotic or Not to Probiotic: A Metagenomic Comparison of the Discharge Gut Microbiome of Infants Supplemented With Probiotics in NICU and Those Who Are Not.

Background: Preterm birth is associated with the development of both acute and chronic disease, and the disruption of normal gut microbiome development. Recent studies have sought to both characterize and understand the links between disease and the microbiome. Probiotic treatment may correct for these microbial imbalances and, in turn, mitigate disease. However, the criteria for probiotic supplementation in NICU's in North Queensland, Australia limits its usage to the most premature (<32 weeks gestation) and small for gestational age infants (<1,500 g). Here we use a combination of amplicon and shotgun metagenomic sequencing to compare the gut microbiome of infants who fulfill the criteria for probiotic-treatment and those who do not. The aims of this study were to determine if probiotic-supplemented preterm infants have significantly different taxonomic and functional profiles when compared to non-supplemented preterm infants at discharge. Methods: Preterm infants were recruited in North Queensland, Australia, with fecal samples collected just prior to discharge (36 ± 0.5 weeks gestation), to capture potential changes that could be probiotic induced. All samples underwent 16S rRNA gene amplicon sequencing, with a subset also used for shotgun metagenomics. Mixed effects models were used to assess the effect of probiotics on alpha diversity, beta diversity and taxonomic abundance, whilst accounting for other known covariates. Results: Mixed effects modeling demonstrated that probiotic treatment had a significant effect on overall community composition (beta diversity), characterized by greater alpha diversity and differing abundances of several taxa, including Bifidobacterium and Lactobacillus, in supplemented infants. Conclusion: Late preterm-infants who go without probiotic-supplementation may be missing out on stabilizing-effects provided through increased alpha diversity and the presence of commensal microbes, via the use of probiotic-treatment. These findings suggest that late-preterm infants may benefit from probiotic supplementation. More research is needed to both understand the consequences of the differences observed and the long-term effects of this probiotic-treatment.

The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge.

BACKGROUND: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. METHODS: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. RESULTS: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. CONCLUSIONS: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. IMPACT: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants.

Impact of physical decontamination methods on zirconia implant surface and subsequent bacterial adhesion: An in-vitro study.

OBJECTIVE: To evaluate the effect of routinely used physical decontamination methods on the surface characteristics of zirconia implants and subsequent ability of bacteria to adhere in vitro. BACKGROUND: Physical decontamination methods commonly used in peri-implantitis therapy and routine implant maintenance can potentially alter zirconia implant surfaces. METHODS: Acid-etched zirconia discs were instrumented with titanium curette (TC), plastic curette, air abrasive device, ultrasonic scaler (US) with stainless steel tip. Following instrumentation, surface topography, and surface elemental composition was analyzed using 3D-laser scanning microscopy and energy-dispersive X-ray spectroscopy, respectively. Subsequently, plaque biofilm was cultured on zirconia discs for 48 h and bacterial adhesion assessed using a turbidity test and scanning electron microscopy. RESULTS: A significant difference in surface roughness was observed between the US and control group (p < 0.05). The US and TC caused gray surface discolouration on zirconia discs due to deposition of metallic residue as confirmed by X-ray spectroscopy. No significant difference in bacterial adhesion was noted among all treatment groups (p > 0.05). CONCLUSION: TC and US with stainless steel tips should be used with caution due to deposition of metallic residue on the surface. Air abrasive devices and plastic curettes caused minimal surface alterations and are, therefore, safer for zirconia implant decontamination.

The effects of physical decontamination methods on zirconia implant surfaces: a systematic review.

PURPOSE: Peri-implantitis therapy and implant maintenance are fundamental practices to enhance the longevity of zirconia implants. However, the use of physical decontamination methods, including hand instruments, polishing devices, ultrasonic scalers, and laser systems, might damage the implant surfaces. The aim of this systematic review was to evaluate the effects of physical decontamination methods on zirconia implant surfaces. METHODS: A systematic search was conducted using 5 electronic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane. Hand searching of the OpenGrey database, reference lists, and 6 selected dental journals was also performed to identify relevant studies satisfying the eligibility criteria. RESULTS: Overall, 1049 unique studies were identified, of which 11 studies were deemed suitable for final review. Air-abrasive devices with glycine powder, prophylaxis cups, and ultrasonic scalers with non-metal tips were found to cause minimal to no damage to implant-grade zirconia surfaces. However, hand instruments and ultrasonic scalers with metal tips have the potential to cause major damage to zirconia surfaces. In terms of laser systems, diode lasers appear to be the most promising, as no surface alterations were reported following their use. CONCLUSION: Air-abrasive devices and prophylaxis cups are safe for zirconia implant decontamination due to preservation of the implant surface integrity. In contrast, hand instruments and ultrasonic scalers with metal tips should be used with caution. Recommendations for the use of laser systems could not be fully established due to significant heterogeneity among included studies, but diode lasers may be the best-suited system. Further research-specifically, randomised controlled trials-would further confirm the effects of physical decontamination methods in a clinical setting.

Methods for exploring the faecal microbiome of premature infants: a review.

The premature infant gut microbiome plays an important part in infant health and development, and recognition of the implications of microbial dysbiosis in premature infants has prompted significant research into these issues. The approaches to designing investigations into microbial populations are many and varied, each with its own benefits and limitations. The technique used can influence results, contributing to heterogeneity across studies. This review aimed to describe the most common techniques used in researching the preterm infant microbiome, detailing their various limitations. The objective was to provide those entering the field with a broad understanding of available methodologies, so that the likely effects of their use can be factored into literature interpretation and future study design. We found that although many techniques are used for characterising the premature infant microbiome, 16S rRNA short amplicon sequencing is the most common. 16S rRNA short amplicon sequencing has several benefits, including high accuracy, discoverability and high throughput capacity. However, this technique has limitations. Each stage of the protocol offers opportunities for the injection of bias. Bias can contribute to variability between studies using 16S rRNA high throughout sequencing. Thus, we recommend that the interpretation of previous results and future study design be given careful consideration.

Control of human toxoplasmosis.

Toxoplasmosis is caused by Toxoplasma gondii, an apicomplexan parasite that is able to infect any nucleated cell in any warm-blooded animal. Toxoplasma gondii infects around 2 billion people and, whilst only a small percentage of infected people will suffer serious disease, the prevalence of the parasite makes it one of the most damaging zoonotic diseases in the world. Toxoplasmosis is a disease with multiple manifestations: it can cause a fatal encephalitis in immunosuppressed people; if first contracted during pregnancy, it can cause miscarriage or congenital defects in the neonate; and it can cause serious ocular disease, even in immunocompetent people. The disease has a complex epidemiology, being transmitted by ingestion of oocysts that are shed in the faeces of definitive feline hosts and contaminate water, soil and crops, or by consumption of intracellular cysts in undercooked meat from intermediate hosts. In this review we examine current and future approaches to control toxoplasmosis, which encompass a variety of measures that target different components of the life cycle of T. gondii. These include: education programs about the parasite and avoidance of contact with infectious stages; biosecurity and sanitation to ensure food and water safety; chemo- and immunotherapeutics to control active infections and disease; prophylactic options to prevent acquisition of infection by livestock and cyst formation in meat; and vaccines to prevent shedding of oocysts by definitive feline hosts.

Treatment of mice with S4B6 IL-2 complex prevents lethal toxoplasmosis via IL-12- and IL-18-dependent interferon-gamma production by non-CD4 immune cells.

Toxoplasmic encephalitis is an AIDS-defining condition. The decline of IFN-γ-producing CD4+ T cells in AIDS is a major contributing factor in reactivation of quiescent Toxoplasma gondii to an actively replicating stage of infection. Hence, it is important to characterize CD4-independent mechanisms that constrain acute T. gondii infection. We investigated the in vivo regulation of IFN-γ production by CD8+ T cells, DN T cells and NK cells in response to acute T. gondii infection. Our data show that processing of IFN-γ by these non-CD4 cells is dependent on both IL-12 and IL-18 and the secretion of bioactive IL-18 in response to T. gondii requires the sensing of viable parasites by multiple redundant inflammasome sensors in multiple hematopoietic cell types. Importantly, our results show that expansion of CD8+ T cells, DN T cells and NK cell by S4B6 IL-2 complex pre-treatment increases survival rates of mice infected with T. gondii and this is dependent on IL-12, IL-18 and IFN-γ. Increased survival is accompanied by reduced pathology but is independent of expansion of TReg cells or parasite burden. This provides evidence for a protective role of IL2C-mediated expansion of non-CD4 cells and may represent a promising lead to adjunct therapy for acute toxoplasmosis.

Interactions of Osteoprogenitor Cells with a Novel Zirconia Implant Surface.

Background: This study compared the in vitro response of a mouse pre-osteoblast cell line on a novel sandblasted zirconia surface with that of titanium. Material and Methods: The MC3T3-E1 subclone 4 osteoblast precursor cell line was cultured on either sandblasted titanium (SBCpTi) or sandblasted zirconia (SBY-TZP). The surface topography was analysed by three-dimensional laser microscopy and scanning electron microscope. The wettability of the discs was also assessed. The cellular response was quantified by assessing the morphology (day 1), proliferation (day 1, 3, 5, 7, 9), viability (day 1, 9), and migration (0, 6, 24 h) assays. Results: The sandblasting surface treatment in both titanium and zirconia increased the surface roughness by rendering a defined surface topography with titanium showing more apparent nano-topography. The wettability of the two surfaces showed no significant difference. The zirconia surface resulted in improved cellular spreading and a significantly increased rate of migration compared to titanium. However, the cellular proliferation and viability noted in our experiments were not significantly different on the zirconia and titanium surfaces. Conclusions: The novel, roughened zirconia surface elicited cellular responses comparable to, or exceeding that, of titanium. Therefore, this novel zirconia surface may be an acceptable substitute for titanium as a dental implant material.

The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.

Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1ß. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1-/- mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites.

Short-term reliability of inflammatory mediators and response to exercise in the heat.

Prospective application of serum cytokines, lipopolysaccharide (LPS), and heat shock proteins (eHSPs) requires reliable measurement of these biomarkers that can signify exercise-induced heat stress in hot conditions. To accomplish this, both short-term (7 day) reliability (at rest, n = 12) and the acute responsiveness of each biomarker to exercise in the heat (pre and post 60-min cycling, 34.5°C and 70% RH, n = 20) were evaluated. Serum was analysed for the concentration of C-reactive protein (CRP), interleukin-6 (IL-6), heat shock protein 72 (eHSP72), immunoglobulin M (IgM) and LPS. Test-retest reliability was determined as the coefficient of variation (CV). Biomarkers with the least short-term within-participant variation were IL-6 (19%, ±20%; CV, ±95% confidence limits (CL)) and LPS (23%, ±13%). Greater variability was observed for IgM, eHSP72 and CRP (CV range 28-38%). IL-6 exhibited the largest increase in response to acute exercise (95%, ±11%, P = < 0.001) and although CRP had a modest CV (12%, ±7%), it increased substantially post-exercise (P = 0.02, ES; 0.78). In contrast, eHSP72 and LPS exhibited trivial changes post-exercise. It appears variation of common inflammatory markers after exercise in the heat is not always discernible from short-term (weekly) variation.

Acclimation Training Improves Endurance Cycling Performance in the Heat without Inducing Endotoxemia.

PURPOSE: While the intention of endurance athletes undertaking short term heat training protocols is to rapidly gain meaningful physical adaption prior to competition in the heat, it is currently unclear whether or not this process also presents an overt, acute challenge to the immune system. The aim of this study was therefore to examine the effects of heat training on both endurance performance and biomarkers associated with inflammatory and immune system responses. METHODS: Moderately-actively males (n = 24) were allocated randomly to either HOT (n = 8, 35°C, and 70% RH; NEUTRAL (n = 8, 20°C, and 45% RH); or a non-exercising control group, (CON, n = 8). Over the 18 day study HOT and NEUTRAL performed seven training sessions (40 min cycling at 55 of VO2 max) and all participants completed three heat stress tests (HST) at 35°C and 70% RH. The HST protocol comprised three × sub-maximal intervals followed by a 5 km time trial on a cycle ergometer. Serum samples were collected before and after each HST and analyzed for interleukin-6, immunoglobulin M and lipopolysaccharide. RESULTS: Both HOT and NEUTRAL groups experienced substantial improvement to 5 km time trial performance (HOT -33 ± 20 s, p = 0.02, NEUTRAL -39 ± 18 s, p = 0.01) but only HOT were faster (-45 ± 25 s, and -12 s ± 7 s, p = 0.01) in HST3 compared to baseline and HST2. Interleukin-6 was elevated after exercise for all groups however there were no significant changes for immunoglobulin M or lipopolysaccharide. CONCLUSIONS: Short-term heat training enhances 5 km cycling time trial performance in moderately-fit subjects by ~6%, similar in magnitude to exercise training in neutral conditions.Three top-up training sessions yielded a further 3% improvement in performance for the HOT group. Furthermore, the heat training did not pose a substantial challenge to the immune system.

Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis.

BACKGROUND: Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. PRINCIPAL FINDINGS: Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. CONCLUSIONS: Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.