Macrophages represent the major pool of IL-7Rα expressing cells in patients with myocarditis

Kubin, Natalia; Richter, Manfred; Sen-Hild, B.; Akintürk, Hakan; Schönburg, Markus; Kubin, Thomas; Cetinkaya, Ayse

doi:10.1016/j.cyto.2020.155053

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…Antibodies are listed in Figure 1(b) used for Western blot analysis, and tissues sections were prepared for confocal microscopy as previously described in detail [ 2 ].…”

Section: Methodsmentioning

confidence: 99%

“…For comparison, 0.2 mg/ml human serum albumin (Sigma) was added to basic medium in the controls. Figure 1(b) used for Western blot analysis, and tissues sections were prepared for confocal microscopy as previously described in detail [2].…”

Section: Preparation Of Serum Control Samples Morphogens Andmentioning

confidence: 99%

“…However, under chronic conditions such as dilated cardiomyopathy, the "status quo" is disturbed and ventricular remodeling occurs which affects the amount and the composition of proteins in cardiac cells and the extracellular matrix. Often, inflammatory processes even at a low grade might continuously contribute to cardiac remodeling by changing the level of cytokines and leukocyte subsets in the tissue as well as in the circulation [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Radixin Relocalization and Nonmuscle α-Actinin Expression Are Features of Remodeling Cardiomyocytes in Adult Patients with Dilated Cardiomyopathy

et al. 2020

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Background. Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling—involving the expression of fetal genes—is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods. NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results. In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions. Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.

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“…Antibodies are listed in Figure 1(b) used for Western blot analysis, and tissues sections were prepared for confocal microscopy as previously described in detail [ 2 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Preparation Of Serum Control Samples Morphogens Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radixin Relocalization and Nonmuscle α-Actinin Expression Are Features of Remodeling Cardiomyocytes in Adult Patients with Dilated Cardiomyopathy

et al. 2020

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“…In addition, in rhesus macaques, both CD68 + and CD163 + macrophages were identified in tissues from the FGT (39). Moreover, CD127 expression was previously reported for mouse intestinal macrophages (26), human CD68 + synovial macrophages (44) or human CD68 + and CD163 + macrophages in cardiac ventricular tissues sampled from patients with myocarditis (51), as well as in vitro monocyte-derived human macrophages (52). Similarly, vaginal CD11c + dendritic cells also express CD127 (Figure S3), suggesting that they can participate in the mucosal response to IL-7 stimulation.…”

Section: Discussionmentioning

confidence: 84%

IL-7-adjuvanted vaginal vaccine elicits strong mucosal immune responses in non-human primates

Logerot

Figueiredo

Charmeteau

et al. 2020

Preprint

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Mucosal immune responses are crucial in protecting against pathogens entering through mucosal surfaces. However, due to difficulties in disrupting the tolerogenic environment associated with mucosa, mucosal immunity remains difficult to stimulate through vaccines and requires appropriate adjuvants. We previously demonstrated that either administered systemically to healthy macaques or locally expressed in the intestinal mucosa of acutely SIV-infected macaques, interleukin-7 (IL-7) triggers chemokine expression and immune cell homing into mucosae, suggesting its important role in the development of mucosal immune responses.We therefore examined whether local delivery of recombinant glycosylated simian IL-7 (rs-IL-7gly) to the vaginal mucosa of rhesus macaques could prepare the lower female genital tract (FGT) for subsequent immunization and act as an efficient mucosal adjuvant.First, we showed that local administration of rs-IL-7gly triggers vaginal overexpression of chemokines and infiltration of mDCs, macrophages, NKs, B- and T-cells in the chorion while MamuLa-DR+ APCs accumulated in the epithelium. Subsequent mucosal anti-DT immunization in macaques resulted in a faster, stronger, and more persistent mucosal antibody response compared to DT-immunization alone. Indeed, we detected robust productions of DT-specific IgAs and IgGs in their vaginal secretions and identified cells secreting DT-specific IgAs in their vaginal mucosa and IgGs in draining lymph nodes.Finally, the expression of chemokines involved in the organization of tertiary lymphoid structures (TLS) was only increased in the vaginal mucosa of IL-7-adjuvanted immunized macaques. Interestingly, TLSs developed around PNAd+ high endothelial venules in their lower FGT sampled 2 weeks after the last immunization.Non-traumatic vaginal administration of rs-IL-7gly prepares the mucosa to respond to subsequent local immunization and allows the development of a strong mucosal immune response in macaques, through the chemokine-dependent recruitment of immune cells, the activation of mDCs and the formation of TLSs. The localization of DT-specific IgA plasma cells in the mucosa argues for their contribution to the production of specific immunoglobulins in the vaginal secretions. Our results highlight the potential of IL-7 as a potent mucosal adjuvant to stimulate the FGT immune system and elicit vaginal antibody responses to local immunization, which is the most promising way to confer protection against many sexually transmitted diseases.

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“…IL-7 is produced by macrophages and dendritic cells, which play an important role in maintaining the stability of the immune system [24,25]. When the body is damaged, such as in the oxidative damage of age-related macular degeneration, the expression level of IL-7 is affected [26].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

Wang

Zhang

et al. 2020

Ophthalmic Res

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Purpose: The purpose of our study was to investigate the profiles of inflammatory cytokines and the macrophage polarization gene in a choroidal neovascularization (CNV) mouse model before and after intravitreal aflibercept treatment. Methods: The CNV mouse model was conducted by laser photocoagulation. A total of 58 cytokines were measured by multiplex mouse cytokine antibody array. The macrophage polarization genes were tested by reverse transcription polymerase chain reaction. The relationship between the cytokines and the CNV lesion area was analyzed by correlation. Results: MIP-1a on day 3 after laser photocoagulation, MCP-5 and Fas-L on day 7, and IL-15 and IL-7 on day 14 were significantly upregulated (p< 0.001, fold change > 10.0). After the intravitreal aflibercept treatment, GM-CSF and MCP-1 on day 3 and TIMP-1 on days 7 and 14 were the most significantly upregulated cytokines (p< 0.001, fold change > 10.0). MIP-1 on day 3, IL-13 and Fas-L on day 7, and Fas-L on day 14 were the most significantly downregulated cytokines after intravitreal aflibercept treatment (p< 0.001, fold change > 5.0). M2 polarization and VEGFA genes were significantly increased in the CNV formation, whereas aflibercept suppressed M2 polarization and VEGFA genes. IL-7 was negatively related to the CNV lesion area on day 14 after intravitreal aflibercept treatment (r = −0.938, p = 0.006). Conclusion: The inflammatory cytokines and the M1/M2 macrophage genes significantly changed in the CNV mouse model. This result suggests that inflammatory cytokines and macrophages play a critical role in the physiopathology of CNV.

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Macrophages represent the major pool of IL-7Rα expressing cells in patients with myocarditis

Cited by 12 publications

References 13 publications

Radixin Relocalization and Nonmuscle α-Actinin Expression Are Features of Remodeling Cardiomyocytes in Adult Patients with Dilated Cardiomyopathy

Radixin Relocalization and Nonmuscle α-Actinin Expression Are Features of Remodeling Cardiomyocytes in Adult Patients with Dilated Cardiomyopathy

IL-7-adjuvanted vaginal vaccine elicits strong mucosal immune responses in non-human primates

Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

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