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Study identifies molecule critical to asthma-causing cell's survival
USC News Scientists led by molecular immunologists at the Keck School of Medicine of USC have identified a way to target a recently discovered cell type that causes asthma, opening the door to cure the chronic respiratory disease that affects 25 million Americans. |
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IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury.
J Am Soc Nephrol. 2015 Jan 2;
Authors: Huang Q, Niu Z, Tan J, Yang J, Liu Y, Ma H, Lee VW, Sun S, Song X, Guo M, Wang Y, Cao Q
Abstract
IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPP(type2)) cells in kidney. IL-25-responsive ILC2 and MPP(type2) cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPP(type2) cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPP(type2) cells regulate macrophage phenotype in kidney and prevent renal IRI.
PMID: 25556172 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.
J Immunol. 2014 Dec 19;
Authors: Böhm L, Maxeiner J, Meyer-Martin H, Reuter S, Finotto S, Klein M, Schild H, Schmitt E, Bopp T, Taube C
Abstract
Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.
PMID: 25527785 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
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Lung-Homing of Endothelial Progenitor Cells and Airway Vascularization Is Only Partially Dependant on Eosinophils in a House Dust Mite-Exposed Mouse Model of Allergic Asthma.
PLoS One. 2014;9(10):e109991
Authors: Sivapalan N, Wattie J, Inman MD, Sehmi R
Abstract
BACKGROUND: Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1), a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC) to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL) whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.
METHODS: Wild-type (WT) BALB/c and eosinophil deficient (PHIL) mice were sensitized to house dust mite (HDM) using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD) and airway methacholine responsiveness (AHR).
RESULTS: Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.
CONCLUSIONS: This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.
PMID: 25279605 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Condition: Duchenne’s Muscular Dystrophy
Intervention: Biological: Umbilical Cord Mesenchymal Stem Cells
Sponsors: Allergy and Asthma Consultants, Wichita, KansasAidan Foundation; Neil H. Riordan PhDAllergy and Asthma Consultants, Wichita, Kansas
Enrolling by invitation – verified September 2014
View full post on ClinicalTrials.gov: asthma | received in the last 14 days
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Vitamin D reduces the differentiation and expansion of Th17 cells in young asthmatic children.
Immunobiology. 2014 Jul 22;
Authors: Hamzaoui A, Berraïes A, Hamdi B, Kaabachi W, Ammar J, Hamzaoui K
Abstract
Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many inflammatory and autoimmune pathologies; however, there is still a lack of data about the effects of administration of vitamin D in immune regulation in young asthmatic patients. In this study, we investigated its inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved. Peripheral blood CD4(+) T cells from 10 asthmatic patients and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow cytometry. Messenger RNA (mRNA) expression of several factors related to Th17 cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow cytometry. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of [25(OH)D3] significantly inhibited Th17 cell differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17 production [P=0.002] and decreased the percentage of CD4(+)IL-17(+) [P=0.007] in young asthmatics. The findings suggest that the inhibitory effect of [25(OH)D3] on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics.
PMID: 25128460 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Conditions: Allergic Asthma; Allergic Rhinitis
Intervention:
Sponsor: Lithuanian University of Health Sciences
Recruiting – verified August 2014
View full post on ClinicalTrials.gov: asthma | received in the last 14 days
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Does ?-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of ?-Hexosaminidase in Mast Cell Granules.
J Immunol. 2014 Jul 11;
Authors: Fukuishi N, Murakami S, Ohno A, Yamanaka N, Matsui N, Fukutsuji K, Yamada S, Itoh K, Akagi M
Abstract
?-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of ?-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC ?-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of ?-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or ?-hexosaminidase gene-deficient (hexb(-/-)-BMMC) mice were transplanted into MC-deficient (WBB6F1/J-Kit(W)/Kit(W-v) [W/W(v)]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/W(v), BL/6-BMMC-reconstituted W/W(v), or hexb(-/-)-BMMC-reconstituted W/W(v) mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/W(v) and hexb(-/-)-BMMC-reconstituted W/W(v) mice than in BL/6 and BL/6-BMMC-reconstituted W/W(v) mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb(-/-)-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb(-/-)-BMMC lysate plus ?-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb(-/-)-BMMC lysate. These findings strongly suggest that MC granule ?-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of ?-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.
PMID: 25015817 [PubMed – as supplied by publisher]
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Type I interferons can block development of allergy- and asthma-driving Th2 cells
News-Medical.net A mechanism that could underlie the development of cells that drive asthma and allergies has been uncovered by immunology researchers at UT-Southwestern Medical Center. Asthma and allergies are both driven by an inappropriate activation of the … |
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NKT cells: the smoking gun in fungal-induced asthma?
Nat Med. 2013 Oct 7;19(10):1210-1211
Authors: Godfrey DI, Pellicci DG, Rossjohn J
PMID: 24100979 [PubMed – as supplied by publisher]
View full post on pubmed: asthma