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- Nelke, C, et al.
(författare)
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High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:20
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation of skeletal muscle is the common feature of idiopathic inflammatory myopathies (IIM). Given the rarity of the disease and potential difficulty of routinely obtaining target tissue, i.e., standardized skeletal muscle, our understanding of immune signatures of the IIM spectrum remains incomplete. Further insight into the immune topography of IIM is needed to determine specific treatment targets according to clinical and immunological phenotypes. Thus, we used high-dimensional flow cytometry to investigate the immune phenotypes of anti-synthetase syndrome (ASyS), dermatomyositis (DM) and inclusion-body myositis (IBM) patients as representative entities of the IIM spectrum and compared them to healthy controls. We studied the CD8, CD4 and B cell compartments in the blood aiming to provide a contemporary overview of the immune topography of the IIM spectrum. ASyS was characterized by altered CD4 composition and expanded T follicular helper cells supporting B cell-mediated autoimmunity. For DM, unsupervised clustering identified expansion of distinct B cell subtypes highly expressing immunoglobulin G4 (IgG4) and CD38. Lastly, terminally differentiated, cytotoxic CD8 T cells distinguish IBM from other IIM. Interestingly, these terminally differentiated CD8 T cells highly expressed the integrin CD18 mediating cellular adhesion and infiltration. The distinct immune cell topography of IIM might provide the framework for targeted treatment approaches potentially improving therapeutic outcomes.
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| 2. |
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| 3. |
- Rossaint, J, et al.
(författare)
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Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education
- 2021
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution. Mechanistically, intravascular platelets form aggregates with T reg cells, a prerequisite for their recruitment into the lung. This interaction relies on platelet activation by sCD40L and platelet P-selectin binding to PSGL-1 on T reg cells. Physical platelet–T reg cell interactions are necessary to modulate the transcriptome and instruct T reg cells to release the anti-inflammatory mediators IL-10 and TGFβ. Notably, the presence of platelet–T reg cell aggregates in the lung was also required for macrophage transcriptional reprogramming, polarization toward an anti-inflammatory phenotype, and effective resolution of pulmonary inflammation. Thus, platelets partner with successive immune cell subsets to orchestrate both the initiation and resolution of inflammation.
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