Molecular mechanisms of the adaptive, innate and regulatory immune responses in the intestinal mucosa of celiac disease patients

The new coronavirus infection has posed a major public health challenge around the world, but new data on the disease raises more questions than answers. The lack of optimal therapy is a significant problem. The article examines the molecular mechanisms of SARS-CoV-2 infection and the pathogenesis of COVID-19, special attention is paid to features of pathological processes and immune responses in children. COVID-19 leads to a wide diversity of negative outcomes, many of which can persist for at least months. Many of the consequences have yet to be identified. SARS-CoV-2 may provoke autoimmune reactions. Reinfection, herd immunity, vaccines and other prevention measures are also discussed in this review.

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Human fetal liver MSCs are more effective than adult bone marrow MSCs for their immunosuppressive, immunomodulatory, and Foxp3+ T reg induction capacity

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02176-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yi Yu ◽

Alejandra Vargas Valderrama ◽

Zhongchao Han ◽

Georges Uzan ◽

Sina Naserian ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Immune Responses ◽

Molecular Mechanisms ◽

Fetal Liver ◽

Cytotoxic T Cells ◽

Cell Contact ◽

Adult Bone Marrow ◽

Adult Bone

Abstract Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.

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Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

International Journal of Molecular Sciences ◽

10.3390/ijms22031201 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1201

Author(s):

Hsuan Peng ◽

Kazuhiro Shindo ◽

Renée R. Donahue ◽

Ahmed Abdel-Latif

Keyword(s):

Stem Cell ◽

Immune Responses ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Clinical Evidence ◽

Current Knowledge ◽

Cell Delivery ◽

Cardiac Cell Therapy ◽

Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

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TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation

Science Advances ◽

10.1126/sciadv.abd4235 ◽

2021 ◽

Vol 7 (3) ◽

pp. eabd4235

Author(s):

P. Pradhan ◽

R. Toy ◽

N. Jhita ◽

A. Atalis ◽

B. Pandey ◽

...

Keyword(s):

Immune Responses ◽

Molecular Mechanisms ◽

Lipid A ◽

Critical Role ◽

Mouse Bone Marrow ◽

Biophysical Properties ◽

Gm Csf ◽

Monophosphoryl Lipid A ◽

Integrated Response ◽

Particulate Carriers

Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF–driven mouse bone marrow–derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)–TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.

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MicroRNAs from Snellenius manilae bracovirus regulate innate and cellular immune responses of its host Spodoptera litura

Communications Biology ◽

10.1038/s42003-020-01563-3 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Cheng-Kang Tang ◽

Chih-Hsuan Tsai ◽

Carol-P. Wu ◽

Yu-Hsien Lin ◽

Sung-Chan Wei ◽

...

Keyword(s):

Immune Responses ◽

Spodoptera Litura ◽

Molecular Mechanisms ◽

Innate Immune ◽

Sequencing Analysis ◽

Innate Immune Responses ◽

Cellular Immune Responses ◽

Next Generation Sequencing Analysis ◽

Cellular Immune ◽

Generation Sequencing

AbstractTo avoid inducing immune and physiological responses in insect hosts, parasitoid wasps have developed several mechanisms to inhibit them during parasitism, including the production of venom, specialized wasp cells, and symbioses with polydnaviruses (PDVs). These mechanisms alter the host physiology to give the wasp offspring a greater chance of survival. However, the molecular mechanisms for most of these alterations remain unclear. In the present study, we applied next-generation sequencing analysis and identified several miRNAs that were encoded in the genome of Snellenius manilae bracovirus (SmBV), and expressed in the host larvae, Spodoptera litura, during parasitism. Among these miRNAs, SmBV-miR-199b-5p and SmBV-miR-2989 were found to target domeless and toll-7 in the host, which are involved in the host innate immune responses. Microinjecting the inhibitors of these two miRNAs into parasitized S. litura larvae not only severely decreased the pupation rate of Snellenius manilae, but also restored the phagocytosis and encapsulation activity of the hemocytes. The results demonstrate that these two SmBV-encoded miRNAs play an important role in suppressing the immune responses of parasitized hosts. Overall, our study uncovers the functions of two SmBV-encoded miRNAs in regulating the host innate immune responses upon wasp parasitism.

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Interrogating Plant-Microbe Interactions with Chemical Tools: Click Chemistry Reagents for Metabolic Labeling and Activity-Based Probes

Molecules ◽

10.3390/molecules26010243 ◽

2021 ◽

Vol 26 (1) ◽

pp. 243

Author(s):

Vivian S. Lin

Keyword(s):

Plant Growth ◽

Immune Responses ◽

Click Chemistry ◽

Chemical Biology ◽

Molecular Mechanisms ◽

Metabolic Labeling ◽

Beneficial Microbes ◽

Plant Hosts ◽

Microbe Interactions ◽

Growth Metabolism

Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes on plant growth, metabolism, and immune responses. While the majority of the studies reviewed here used chemical biology approaches to examine the effects of pathogens on plants, chemical biology will also be invaluable in future efforts to investigate mutualistic associations between beneficial microbes and their plant hosts.

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Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines

Microorganisms ◽

10.3390/microorganisms9040683 ◽

2021 ◽

Vol 9 (4) ◽

pp. 683

Author(s):

Julio Villena ◽

Chang Li ◽

Maria Guadalupe Vizoso-Pinto ◽

Jacinto Sacur ◽

Linzhu Ren ◽

...

Keyword(s):

Immune Responses ◽

Oral Administration ◽

Molecular Mechanisms ◽

Spike Protein ◽

Heterologous Proteins ◽

Oral Vaccines ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Viral Antigens ◽

Mucosal Infection

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacillus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.

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Contribution of Infectious Agents to the Development of Celiac Disease

Microorganisms ◽

10.3390/microorganisms9030547 ◽

2021 ◽

Vol 9 (3) ◽

pp. 547

Author(s):

Daniel Sánchez ◽

Iva Hoffmanová ◽

Adéla Szczepanková ◽

Věra Hábová ◽

Helena Tlaskalová-Hogenová

Keyword(s):

Celiac Disease ◽

Intestinal Mucosa ◽

Wheat Gluten ◽

Small Intestinal Mucosa ◽

Beneficial Effects ◽

Immune Mediated ◽

Healthy State ◽

Food Antigens ◽

Small Intestinal ◽

And Function

The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.

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Magnifying endoscopy of the duodenum with dye scattering method in a case with celiac disease

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032003000200009 ◽

2003 ◽

Vol 40 (2) ◽

pp. 110-113 ◽

Cited By ~ 2

Author(s):

Tetsuo Morishita ◽

Toshiaki Kamiya ◽

Hiromasa Ishii

Keyword(s):

Celiac Disease ◽

Intestinal Mucosa ◽

Indigo Carmine ◽

Duodenal Mucosa ◽

Magnifying Endoscopy ◽

Scattering Method ◽

Small Intestinal Mucosa ◽

Before And After ◽

Dye Scattering Method ◽

Magnifying Endoscope

AIM: To know the more detailed findings of the small intestinal mucosa with the use of a magnifying endoscope and a vital dye, and the efficacy of the both tools. PATIENT AND METHODS: A 54-year old female patient with celiac disease. The duodenal mucosa downward as far as the descending portion was observed with a magnifying endoscope (Olympus GIF HM) before and after spraying the mucosa with 0.1% indigo carmine. RESULTS: The endoscopy clarified the atrophy and edema of each villus, and scattering of the dye revealed shorter villi with the relatively longer villi remaining in islands. CONCLUSION: The combination of magnifying endoscopy and the dye scattering method is useful for closer observation of the intestinal mucosa in celiac diseases.

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Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response

BioMed Research International ◽

10.1155/2019/3494937 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Muhammad M. Aslam ◽

Peter John ◽

Attya Bhatti ◽

Sidrah Jahangir ◽

M. I. Kamboh

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Immune Responses ◽

Molecular Mechanisms ◽

Genetic Factors ◽

Autoimmune Disorder ◽

Serum Levels ◽

Principal Factor ◽

Phosphate Homeostasis ◽

Low Serum

Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.

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