Synovial fluid (SF)-derived monocyte-macrophage (MON-Mφ)-lineage cells in knee osteoarthritis (KOA) remain poorly understood. We analyzed SF samples from 420 patients with KOA with effusion. The MON-Mφ cells accounted for 47.4% (median; range 7.1%-94.4%) of CD45+ cells and consisted of four subpopulations that correlated with the distribution and activation of other immune cells. The most abundant subpopulation was that of inactive CD11b+CD14-CD16- myeloid dendritic cells (mDCs; cDC2), which exhibited low cytokine production, low T lymphocyte stimulation, and high migratory ability. Other major subpopulations included CD11b+CD14+CD16- monocyte-like cells and CD11b+CD14+CD16+ macrophages, which share a similar transcriptomic profile. A subpopulation of CD11b-CD14-CD16- mDCs (cDC1) was less common. A higher proportion of CD11b+CD14-CD16- mDCs was linked to early-stage KOA and mild joint pain. Dendritic cells were rarely present in KOA synovium. This study revealed the considerable complexity of SF-derived MON-Mφ subpopulations and highlighted the role of inactive mDCs in KOA.

• MeSH
• artróza kolenních kloubů * patologie   metabolismus   imunologie   MeSH
• buněčný rodokmen MeSH
• dendritické buňky * metabolismus   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy * metabolismus   imunologie   MeSH
• monocyty * metabolismus   imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• synoviální tekutina * metabolismus   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli cells can play immunomodulatory role in tadpole tail regeneration and can thus benefit the regeneration process are needed to be discovered. METHODS: Immature Sertoli cells from Xenopus tropicalis (XtiSCs) were transplanted into X. tropicalis tadpoles, followed by the amputation of the final third of their tails. We assessed the migration of XtiSCs, tail regeneration length, muscle degradation and growth, and macrophage counts across various regions including the entire tail, tail trunk, injection site, and regeneration site. The interactions between XtiSCs and macrophages were examined using a confocal microscope. To deplete macrophages, clodronate liposomes were administered prior to the transplantation of XtiSCs, while the administration of control liposomes acted as a negative control. Student's t-test was used to compare the effects of XtiSCs injection to those of a 2/3PBS injection across groups with no liposomes, control liposomes, and clodronate liposomes. RESULTS: XtiSCs have excellent viability after transplantation to tadpole tail and remarkable homing capabilities to the regeneration site after tail amputation. XtiSCs injection increased macrophage numbers at 3 days post-amputation and 5 days post-amputation in the tail trunk, specifically at the injection site and at the regenerated tail, in a macrophage depleted environment (clodronate-liposome injection). What's more, XtiSCs injection decreased muscle fibers degradation significantly at 1 day post-amputation and facilitated new muscle growth significantly at 3 days post-amputation. In addition, whole-mount immunostaining showed that some XtiSCs co-localized with macrophages. And we observed potential mitochondria transport from XtiSCs to macrophages using MitoTracker staining in tadpole tail. CONCLUSIONS: Our study delineates the novel role of XtiSCs in facilitating muscle regeneration post tadpole tail amputation, underscoring a unique interaction with macrophages that is crucial for regenerative success. This study not only highlights the therapeutic potential of Sertoli cells in regenerative medicine but also opens avenues for clinical translation, offering insights into immunoregulatory strategies that could enhance tissue regeneration and transplant acceptance.

• MeSH
• imunomodulace MeSH
• larva * MeSH
• makrofágy * metabolismus   imunologie   MeSH
• ocas MeSH
• regenerace * MeSH
• Sertoliho buňky * cytologie   metabolismus   MeSH
• Xenopus * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17+ γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets.

• MeSH
• dendritické buňky imunologie   MeSH
• interleukin 33 * metabolismus   imunologie   MeSH
• kůže imunologie   parazitologie   MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• myeloidní buňky imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• neurony imunologie   metabolismus   MeSH
• pruritus imunologie   MeSH
• receptory spřažené s G-proteiny * metabolismus   imunologie   genetika   MeSH
• Schistosoma mansoni * imunologie   MeSH
• schistosomiasis mansoni * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• interferon gama genetika   imunologie   MeSH
• Leishmania braziliensis imunologie   MeSH
• Leishmania donovani imunologie   MeSH
• Leishmania major imunologie   MeSH
• leishmanióza kožní imunologie   patologie   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• monocyty imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přirozená imunita genetika   imunologie   MeSH
• proteiny vázající GTP genetika   metabolismus   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• COVID-19 * imunologie   MeSH
• exprese genu imunologie   MeSH
• inflamasomy * imunologie   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• protein S imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinická studie MeSH

The project is focused on the study of innate immune mechanisms in kidney transplantation. The parameters of human monocytes activation will be studied in early post-transplant period and in treatment complications (delayed graft function/rejection/infection). Soluble forms of myeloid antigens (sCD14, sCD163, S100A8/S100A9) will be monitored in kidney transplant patients as potential biomarkers of monocyte/macrophage activation, in the case of complications, proportions of monocytes subpopulations CD14+CD16+ and CD14+CD163+ in peripheral blood will be also evaluated. Using an co-culture model, the effect of macrophages on renal epithelial activation (gene induction and release of cytokines, expression of activation membrane markers) and reparative ability (renewal of mechanicaly damaged monolayer) will be studied. Furthermore, mRNA markers of monocyte activation in a co-culture with autologous v.s. allogenic v.s. xenogenic cells will be tested to asses potential allo (xeno-) reactivity of innate immune cells.

Projekt je zaměřen na studium mechanismů přirozené imunity u transplantací ledvin. Studovány budou parametry aktivace lidských monocytů v časném potransplantačním období a při komplikacích léčby (oddálená funkce štěpu/rejekce/infekce). U pacientů po transplantaci ledviny budou monitorovány solubilní formy myeloidních antigenů (sCD14, sCD163, S1008/S10014) jako potenciální biomarkery aktivace monocytů a makrofágů, v průběhu komplikací léčby bude vyšetřováno také zastoupení monocytárních subpopulací CD14+CD16+ a CD14+CD163+ v periferní krvi. Na tkáňovém modelu bude sledován vliv ko-kultivovaných makrofágů na aktivaci (indukce genů a sekrece prozánětlivých cytokinů, exprese aktivačních membránových znaků) renálních epiteliálních buněk a na jejich reparační schopnosti (rychlost obnovy mechanicky porušené konfluentní vrstvy). Dále budou porovnávány na úrovni mRNA známky aktivace monocytů při kokultivaci s autologními vs. allogenními v.s. xenogenními buňkami za účelem posoudit možnost jejich případné allo- či xeno-reaktivity.

• MeSH
• biologické markery MeSH
• epitelové buňky imunologie   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• monocyty imunologie   MeSH
• přirozená imunita MeSH
• rejekce štěpu imunologie   MeSH
• transplantace ledvin MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• transplantologie
• alergologie a imunologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

• MeSH
• adaptivní imunita * MeSH
• beta-glukany metabolismus   MeSH
• buněčná imunita MeSH
• buňky NK imunologie   metabolismus   MeSH
• homeostáza imunologie   MeSH
• leukocyty imunologie   metabolismus   MeSH
• lidé MeSH
• lymfocyty imunologie   metabolismus   MeSH
• makrofágy imunologie   metabolismus   MeSH
• monocyty imunologie   metabolismus   MeSH
• náchylnost k nemoci MeSH
• přirozená imunita * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

• MeSH
• aktivace makrofágů genetika   imunologie   MeSH
• biologické markery MeSH
• biologické modely MeSH
• cytokiny metabolismus   MeSH
• exozómy metabolismus   MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• mikro RNA genetika   MeSH
• náchylnost k nemoci * MeSH
• plasticita buňky MeSH
• plicní fibróza etiologie   metabolismus   patologie   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

LST1 is a small adaptor protein expressed in leukocytes of myeloid lineage. Due to the binding to protein tyrosine phosphatases SHP1 and SHP2 it was thought to have negative regulatory function in leukocyte signaling. It was also shown to be involved in cytoskeleton regulation and generation of tunneling nanotubes. LST1 gene is located in MHCIII locus close to many immunologically relevant genes. In addition, its expression increases under inflammatory conditions such as viral infection, rheumatoid arthritis and inflammatory bowel disease and its deficiency was shown to result in slightly increased sensitivity to influenza infection in mice. However, little else is known about its role in the immune system homeostasis and immune response. Here we show that similar to humans, LST1 is expressed in mice in the cells of the myeloid lineage. In vivo, its deficiency results in alterations in multiple leukocyte subset abundance in steady state and under inflammatory conditions. Moreover, LST1-deficient mice show significant level of resistance to dextran sodium sulphate (DSS) induced acute colitis, a model of inflammatory bowel disease. These data demonstrate that LST1 regulates leukocyte abundance in lymphoid organs and inflammatory response in the gut.

• MeSH
• biologické markery MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• fosforylace MeSH
• genotyp MeSH
• intracelulární signální peptidy a proteiny genetika   metabolismus   MeSH
• kolitida etiologie   metabolismus   patologie   MeSH
• leukocyty imunologie   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy imunologie   MeSH
• makrofágy imunologie   metabolismus   MeSH
• membránové proteiny genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• regulace genové exprese * MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Endarterectomy specimens represent a unique opportunity to study atherosclerosis. This review aims to summarize the recent knowledge of atherogenesis from studies characterizing a cellular composition of carotid endarterectomy specimens. EVIDENCE ACQUISITION: A non-systematic literature review was carried out to summarize recent knowledge regarding ex vivo analysis of carotid artery plaque composition. Upon evaluation of their relevance, and elaborate forward and backward search, 95 articles were included in the review. EVIDENCE SYNTHESIS: Despite the significant advancement of in vivo imaging techniques, the stroke prediction based on carotid artery plaque morphology is not reliable. Besides analyses of plaque morphology, present studies focus on precise characterization of the different immune cell types and elucidation of their role in plaque development. Plaque content analyses revealed the presence of various immune cells in carotid artery plaques. Presence of different immune cells subpopulations can be connected to some undesirable changes in plaque stability. CONCLUSIONS: Since the destabilization of the atherosclerotic plaque is a multifactorial process, a combination of various methods should be used to characterize the unstable plaques more accurately. In this context, studies characterizing plaque content from a cellular point of view could elucidate some processes underlying the plaque progression. Together with morphological evaluation, these analyses could enable more precise assessment of plaque stability.

• MeSH
• aterosklerotický plát patologie   MeSH
• ateroskleróza imunologie   patologie   chirurgie   MeSH
• CD antigeny analýza   MeSH
• imunohistochemie MeSH
• karotická endarterektomie MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• průtoková cytometrie MeSH
• stenóza arteria carotis imunologie   patologie   chirurgie   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH