Emerging Roles of Disabled Homolog 2 (DAB2) in Immune Regulation

Paz, Vanessa Figliuolo da; Ghishan, Fayez K.; Kiela, Pawel R.

doi:10.3389/fimmu.2020.580302

Cited by 34 publications

(24 citation statements)

References 68 publications

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“…an increase) [ 72 ], where in parasitic diseases like schistosomiasis, an increase in IL-6 may promote Th2 differentiation and inhibit Th1 polarization [ 73 ]. In addition, the upregulation of Disabled homolog 2 ( Dab2 ) may facilitate Treg-mediated immunosuppression in response to infection; a downregulation of this protein has been linked with a pro-inflammatory switch [ 74 , 75 ]. Consistent with granuloma formation, an increase in U4/U6 small nuclear ribonucleoprotein Prp3 ( Prpf3 ) has been linked with infiltration of macrophages, neutrophils, dendritic cells, and T-cells [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

et al. 2022

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Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology are not well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry. We demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection. S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.

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Section: Discussionmentioning

confidence: 99%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

et al. 2022

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“…an increase) [71], where in parasitic diseases like schistosomiasis, an increase in IL-6 may promote Th2 differentiation and inhibit Th1 polarization [72]. In addition, the upregulation of Disabled homolog 2 (Dab2) may facilitate Treg-mediated immunosuppression in response to infection; a downregulation of this protein has been linked with a pro-inflammatory switch [73,74].…”

Section: Discussionmentioning

confidence: 99%

“…an increase) [75], where in parasitic diseases like schistosomiasis, an increase in IL-6 may promote Th2 differentiation and inhibit Th1 polarization [76]. In addition, the upregulation of Disabled homolog 2 ( Dab2 ) may facilitate Treg-mediated immunosuppression in response to infection; a downregulation of this protein has been linked with a pro-inflammatory switch [77, 78]. Consistent with granuloma formation, an increase in U4/U6 small nuclear ribonucleoprotein Prp3 ( Prpf3 ) has been linked with infiltration of macrophages, neutrophils, dendritic cells, and T-cells [51].…”

Section: Discussionmentioning

confidence: 99%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Osakunor

Ishida

Lamanna

et al. 2021

Preprint

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BackgroundUrogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology have not been well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology.MethodsPurified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry.ResultsWe demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection.ConclusionS. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.Author summaryThe molecular mechanisms underlying the urinary and genital pathology from urogenital schistosomiasis have not been well-defined. This has mainly been due to limited mechanistic studies and the lack of a suitable animal model for S. haematobium infection. We leveraged a mouse model of urogenital schistosomiasis, along with proteomics analysis, to determine the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to define protein pathways that may be involved in morbidity from urogenital schistosomiasis infection. Our results show that S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism are significantly enriched in S. haematobium infection. Our findings highlight important protein indicators of host-parasite interactions in the bladder and their association with tissue changes in urogenital schistosomiasis. The findings presented here will be relevant for development of improved interventions for disease control, and contribute to realizing the 2021-2030 NTD goals by demonstrating evidence on the early events that occur during schistosome infection..

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“…Disabled‐2 (DAB2) is an endocytic adaptor protein that exerts multifaceted roles ranging from cell proliferation and differentiation to innate and adaptive immune responses 12 . In the immune system, DAB2, a target gene of the transcription factor forkhead box P3 (Foxp3), can maintain the function of Treg cells 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Disabled-2 (DAB2) is an endocytic adaptor protein that exerts multifaceted roles ranging from cell proliferation and differentiation to innate and adaptive immune responses. 12 In the immune system, DAB2, a target gene of the transcription factor forkhead box P3 (Foxp3), can maintain the function of Treg cells. 13 DAB2 deficiency contributes to the transformation of colonic dendritic cells to inflammatory Th1/Th17 phenotype and promotes the release of inflammatory factors tumour necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-17A, whereas overexpression of DAB2 contributes to the opposite effects.…”

mentioning

confidence: 99%

Disabled‐2 overexpression mediates immune suppression in systemic lupus erythematosus by modulating Treg/Th17 cell differentiation

Zhang

Chang

Sun

et al. 2022

Clin Exp Pharma Physio

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Systemic lupus erythematosus (SLE) is a common chronic autoimmune disorder characterized by a myriad immune abnormalities and multi-system organ failure. 1,2 At present, immunosuppressive drugs including glucocorticoids and IMID azathioprine are used for the treatment of severe SLE; however, the side effects of them are obvious. 3 Although the specific pathogenesis of SLE is not well elucidated, a variety of types of immune cells have been proposed to be implicated.

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Emerging Roles of Disabled Homolog 2 (DAB2) in Immune Regulation

Cited by 34 publications

References 68 publications

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Disabled‐2 overexpression mediates immune suppression in systemic lupus erythematosus by modulating Treg/Th17 cell differentiation

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