scholarly journals IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent

2013 ◽  
Vol 304 (4) ◽  
pp. G381-G389 ◽  
Author(s):  
Zhonghan Yang ◽  
Rex Sun ◽  
Viktoriya Grinchuk ◽  
Joan Antoni Fernandez Blanco ◽  
Luigi Notari ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Alternative Activation ◽  
Intestinal Immunity ◽  
Intestinal Function ◽  
Mucosal Permeability ◽  
Underlying Mechanisms ◽  
And Function

IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical “type 2” immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected with recombinant IL-33 exhibited intestinal smooth muscle hypercontractility, decreased epithelial responses to acetylcholine and glucose, and increased mucosal permeability. IL-33 effects on intestinal epithelial function were STAT6 dependent, and both IL-4 and IL-13 appeared to play a role. The effects on smooth muscle function, however, were attributable to both STAT6-dependent and -independent mechanisms. In addition, IL-13 induction of insulin-like growth factor-1 was implicated in IL-33-induced smooth muscle hypertrophy. Finally, alternative activation of macrophages induced by IL-33 revealed a novel pathway that is IL-4, IL-13, and STAT6 independent. Thus manipulating IL-33 or related signaling pathways represents a potential therapeutic strategy for treating inflammatory diseases associated with dysregulated intestinal function.

scholarly journals The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Yang ◽  
Xinning Guo ◽  
Tingxuan Huang ◽  
Chuntao Liu
Keyword(s):  
Respiratory Infections ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Intestinal Immunity ◽  
Group 3 ◽  
Underlying Mechanisms ◽  
And Function ◽  
Pathogen Clearance

The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen clearance. In recent years, group 3 innate lymphoid cells (ILC3s) have emerged as key mediators of mucosal protection and repair during infection, mainly through IL-17 and IL-22 production. Although research on ILC3s has become focused on the intestinal immunity, the biology and function of pulmonary ILC3s in the pathogenesis of respiratory infections and in the development of chronic pulmonary inflammatory diseases remain elusive. In this review, we will mainly discuss how pulmonary ILC3s act on protection against pathogen challenge and pulmonary inflammation, as well as the underlying mechanisms.

The Effect of Natural Soluble Polysaccharides On the Type 2 Diabetes through Modulating Gut Microbiota:A review

2021 ◽  
Vol 28 ◽  
Author(s):  
Lina Yang ◽  
Li Li ◽  
Xinghui Wu ◽  
Wenqi Cai ◽  
Qian Lin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Diabetes Management ◽  
Biological Activities ◽  
Short Chain Fatty Acids ◽  
Diabetic Patients ◽  
Gut Health ◽  
Pathogen Invasion ◽  
Underlying Mechanisms

: Diabetes strongly influences patient quality of life. The incidence of type 2 diabetes (T2D) accounts for approximately 90% of diabetic patients. Natural polysaccharides have been widely used for diabetes management. Changes in gut microbiota can also be used for the prevention and treatment of diabetes. In this review, the effects of different natural polysaccharides on gut microbiota, as well as the relationship between diabetes and the gut microbiome are summarized. The intestine is the primary location in which natural polysaccharides exert their biological activities, and plays an important role in maintaining healthy bodily functions. Polysaccharides change the composition of the gut microbiota, which inhibits pathogen invasion and promotes beneficial bacterial growth. In addition, the gut microbiota degrade polysaccharides and produce metabolites to further modify the intestinal environment. Interestingly, the metabolites (short chain fatty acids and other bioactive components) have been shown to improve gut health, control glycemia, lower lipids, reduce insulin resistance, and alleviate inflammation. Therefore, understanding the underlying mechanisms by which soluble polysaccharides improve T2D through regulating the gut microbiota to provide a future reference for the management of T2D and its associated complications.

scholarly journals AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog,Agalychnis callidryas

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lilin Ge ◽  
Peng Lyu ◽  
Mei Zhou ◽  
Huiling Zhang ◽  
Yuantai Wan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Biological Activities ◽  
Antimicrobial Activities ◽  
Skin Secretion ◽  
Bladder Smooth Muscle ◽  
Amphibian Skin ◽  
Pharmacological Characterization ◽  
Rat Urinary Bladder ◽  
Agalychnis Callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog,Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50= 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50= 9.3 μM). The peptide could also inhibit the growth of the microorganisms,Staphylococcus aureus, (MIC = 256 mg/L)Escherichia coli(MIC = 512 mg/L), andCandida albicans(128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

scholarly journals The Role of Regulatory T Cells in the Regulation of Upper Airway Inflammation

2017 ◽  
Vol 31 (6) ◽  
pp. 345-351 ◽  
Author(s):  
Charlie Palmer ◽  
Jennifer K. Mulligan ◽  
Sarah E. Smith ◽  
Carl Atkinson
Keyword(s):  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Upper Airway ◽  
Cell Types ◽  
Inflammatory Cytokine Production ◽  
And Function ◽  
Immunologic Profile ◽  
Type 2 Inflammation

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are inflammatory diseases of the upper airway, with a similar immunologic profile, characterized by aberrant and persistent type 2 inflammation. One cell population that has been identified as altered in both disease types is regulatory T cell (Treg). Tregs have the capacity to modulate T-effector function and suppress inflammatory cytokine production in a broad range of cell types. Given the ability of Tregs to control inflammation, the role of Tregs in respiratory diseases has attracted much attention. As discussed in this article, alterations in the Treg numbers and function, or both, have been identified in AR and CRSwNP, although much of the data is conflicting. Here, we explored what is known and, in many cases, unknown about the mechanisms by which Tregs differentiate and function, and how these functions can be controlled in the mucosal microenvironment. By gaining a greater understanding of these processes, it may be possible to harness the natural immunosuppressive activity of Tregs to ameliorate the chronic inflammation associated with AR and CRSwNP.

scholarly journals Keep calm: the intestinal barrier at the interface of peace and war

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Lester Thoo ◽  
Mario Noti ◽  
Philippe Krebs
Keyword(s):  
Inflammatory Diseases ◽  
Pathological Condition ◽  
Treatment Strategies ◽  
Intestinal Barrier ◽  
Cell Types ◽  
Epithelial Barrier ◽  
Barrier Integrity ◽  
Epithelial Barriers ◽  
Underlying Mechanisms ◽  
And Function

Abstract Epithelial barriers have to constantly cope with both harmless and harmful stimuli. The epithelial barrier therefore serves as a dynamic and not static wall to safeguard its proper physiological function while ensuring protection. This is achieved through multiple defence mechanisms involving various cell types - epithelial and non-epithelial - that work in an integrated manner to build protective barriers at mucosal sites. Damage may nevertheless occur, due to pathogens, physical insults or dysregulated immune responses, which trigger a physiologic acute or a pathologic chronic inflammatory cascade. Inflammation is often viewed as a pathological condition, particularly due to the increasing prevalence of chronic inflammatory (intestinal) diseases. However, inflammation is also necessary for wound healing. The aetiology of chronic inflammatory diseases is incompletely understood and identification of the underlying mechanisms would reveal additional therapeutic approaches. Resolution is an active host response to end ongoing inflammation but its relevance is under-appreciated. Currently, most therapies aim at dampening inflammation at damaged mucosal sites, yet these approaches do not efficiently shut down the inflammation process nor repair the epithelial barrier. Therefore, future treatment strategies should also promote the resolution phase. Yet, the task of repairing the barrier can be an arduous endeavour considering its multiple integrated layers of defence - which is advantageous for damage prevention but becomes challenging to repair at multiple levels. In this review, using the intestines as a model epithelial organ and barrier paradigm, we describe the consequences of chronic inflammation and highlight the importance of the mucosae to engage resolving processes to restore epithelial barrier integrity and function. We further discuss the contribution of pre-mRNA alternative splicing to barrier integrity and intestinal homeostasis. Following discussions on current open questions and challenges, we propose a model in which resolution of inflammation represents a key mechanism for the restoration of epithelial integrity and function.

scholarly journals Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance

2016 ◽  
Vol 84 (4) ◽  
pp. 1032-1044 ◽  
Author(s):  
Rex Sun ◽  
Joseph F. Urban ◽  
Luigi Notari ◽  
Tim Vanuytsel ◽  
Kathleen B. Madden ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Function ◽  
Gastrointestinal Nematode ◽  
Interleukin 4 ◽  
Functional Responses ◽  
Mucosal Permeability ◽  
Alternatively Activated Macrophages ◽  
Content Type ◽  
Smooth Muscle Function

Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1−/−) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasiteHeligmosomoides bakeri. There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1−/−mice. Goblet cell numbers and resistin-like molecule beta (RELM-β) expression were attenuated significantly in IL-13Rα1−/−mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1−/−mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.

scholarly journals Molecular Crosstalk Between Macrophages and Mesenchymal Stromal Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Hazel Y. Stevens ◽  
Annie C. Bowles ◽  
Carolyn Yeago ◽  
Krishnendu Roy
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Inflammatory Diseases ◽  
The Body ◽  
Alternative Activation ◽  
Molecular Alterations ◽  
Preclinical Trials ◽  
And Function

Mesenchymal stromal cells (MSCs) have been widely investigated for regenerative medicine applications, from treating various inflammatory diseases as a cell therapy to generating engineered tissue constructs. Numerous studies have evaluated the potential effects of MSCs following therapeutic administration. By responding to their surrounding microenvironment, MSCs may mediate immunomodulatory effects through various mechanisms that directly (i.e., contact-dependent) or indirectly (i.e., paracrine activity) alter the physiology of endogenous cells in various disease pathologies. More specifically, a pivotal crosstalk between MSCs and tissue-resident macrophages and monocytes (TMφ) has been elucidated using in vitro and in vivo preclinical studies. An improved understanding of this crosstalk could help elucidate potential mechanisms of action (MOAs) of therapeutically administered MSCs. TMφ, by nature of their remarkable functional plasticity and prevalence within the body, are uniquely positioned as critical modulators of the immune system – not only in maintaining homeostasis but also during pathogenesis. This has prompted further exploration into the cellular and molecular alterations to TMφ mediated by MSCs. In vitro assays and in vivo preclinical trials have identified key interactions mediated by MSCs that polarize the responses of TMφ from a pro-inflammatory (i.e., classical activation) to a more anti-inflammatory/reparative (i.e., alternative activation) phenotype and function. In this review, we describe physiological and pathological TMφ functions in response to various stimuli and discuss the evidence that suggest specific mechanisms through which MSCs may modulate TMφ phenotypes and functions, including paracrine interactions (e.g., secretome and extracellular vesicles), nanotube-mediated intercellular exchange, bioenergetics, and engulfment by macrophages. Continued efforts to elucidate this pivotal crosstalk may offer an improved understanding of the immunomodulatory capacity of MSCs and inform the development and testing of potential MOAs to support the therapeutic use of MSCs and MSC-derived products in various diseases.

scholarly journals Altered reactivity of resistance vasculature contributes to hypertension in elastin insufficiency

2014 ◽  
Vol 306 (5) ◽  
pp. H654-H666 ◽  
Author(s):  
Patrick Osei-Owusu ◽  
Russell H. Knutsen ◽  
Beth A. Kozel ◽  
Hans H. Dietrich ◽  
Kendall J. Blumer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Structural Changes ◽  
Rho Kinase ◽  
Ang Ii ◽  
Protein Signaling ◽  
Resistance Arteries ◽  
Increased Sensitivity ◽  
And Function

Elastin ( Eln) insufficiency in mice and humans is associated with hypertension and altered structure and mechanical properties of large arteries. However, it is not known to what extent functional or structural changes in resistance arteries contribute to the elevated blood pressure that is characteristic of Eln insufficiency. Here, we investigated how Eln insufficiency affects the structure and function of the resistance vasculature. A functional profile of resistance vasculature in Eln+/− mice was generated by assessing small mesenteric artery (MA) contractile and vasodilatory responses to vasoactive agents. We found that Eln haploinsufficiency had a modest effect on phenylephrine-induced vasoconstriction, whereas ANG II-evoked vasoconstriction was markedly increased. Blockade of ANG II type 2 receptors with PD-123319 or modulation of Rho kinase activity with the inhibitor Y-27632 attenuated the augmented vasoconstriction, whereas acute Y-27632 administration normalized blood pressure in Eln+/− mice. Sodium nitroprusside- and isoproterenol-induced vasodilatation were normal, whereas ACh-induced vasodilatation was severely impaired in Eln+/− MAs. Histologically, the number of smooth muscle layers did not change in Eln+/− MAs; however, an additional discontinuous layer of Eln appeared between the smooth muscle layers that was absent in wild-type arteries. We conclude that high blood pressure arising from Eln insufficiency is due partly to permanent changes in vascular tone as a result of increased sensitivity of the resistance vasculature to circulating ANG II and to impaired vasodilatory mechanisms arising from endothelial dysfunction characterized by impaired endothelium-dependent vasodilatation. Eln insufficiency causes augmented ANG II-induced vasoconstriction in part through a novel mechanism that facilitates contraction evoked by ANG II type 2 receptors and altered G protein signaling.

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