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
Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppression and tolerance, they will be further referred to as myeloid regulatory cells (MRCs). In recent years, MRCs have emerged as a therapeutic target or have been regarded as a potential cellular therapeutic product for tolerance induction. However, several open questions must be addressed to enable the therapeutic application of MRCs including: how do they function at the site of inflammation, how to best target these cells to modulate their activities, and how to isolate or to generate pure populations for adoptive cell therapies. In this review, we will give an overview of the current knowledge on MRCs in inflammation, autoimmunity, and transplantation. We will discuss current strategies to target MRCs and to exploit their tolerogenic potential as a cell-based therapy.
- MeSH
- autoimunita * MeSH
- biologické markery MeSH
- homeostáza * MeSH
- homologní transplantace MeSH
- imunofenotypizace MeSH
- imunologická tolerance * MeSH
- imunomodulace MeSH
- lidé MeSH
- makrofágy imunologie metabolismus MeSH
- monocyty imunologie metabolismus MeSH
- myeloidní buňky imunologie metabolismus MeSH
- náchylnost k nemoci MeSH
- neutrofily imunologie metabolismus MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- transplantace orgánů MeSH
- zánět etiologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chighMHCII+ cells (Cnb1 CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.
- MeSH
- antigeny CD11c genetika imunologie MeSH
- buňky Th17 imunologie MeSH
- geny MHC třídy II MeSH
- homeostáza MeSH
- interleukin-2 genetika imunologie MeSH
- kalcineurin genetika imunologie MeSH
- kolitida genetika imunologie MeSH
- lidé MeSH
- myeloidní buňky imunologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- střeva imunologie MeSH
- Th1 buňky imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Adipose tissue (AT) lies at the crossroad of nutrition, metabolism, and immunity; AT inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. Resident immune cells constitute the second largest AT cellular component after adipocytes and as such play important roles in the maintenance of AT homeostasis. Obesity-induced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple adiposity to diseases such as type 2 diabetes mellitus, arterial hypertension, and ischemic heart disease. This review has focused on the various subsets of immune cells in AT and their role in the development of AT inflammation and obesity-induced insulin resistance.
- MeSH
- inzulinová rezistence imunologie MeSH
- lidé MeSH
- lymfocyty imunologie patologie MeSH
- myeloidní buňky imunologie patologie MeSH
- obezita etiologie imunologie patologie MeSH
- tuková tkáň imunologie metabolismus patologie MeSH
- zánět etiologie imunologie patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.
- MeSH
- aktivace lymfocytů imunologie MeSH
- antigeny CD45 metabolismus MeSH
- CD antigeny metabolismus MeSH
- dendritické buňky imunologie MeSH
- dospělí MeSH
- imunoglobuliny metabolismus MeSH
- karcinom z renálních buněk imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny metabolismus MeSH
- myeloidní buňky imunologie MeSH
- nádorové mikroprostředí imunologie MeSH
- nádory ledvin imunologie MeSH
- neutrofily imunologie MeSH
- počet lymfocytů MeSH
- regulační T-lymfocyty imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape from antitumor immunity. MDSC accumulate in the lymphoid organs and blood during tumor growth and their mobilization was also reported after cyclophosphamide (CY) administration. In this communication, spleen MDSC accumulating after CY therapy (CY-MDSC) were compared with those expanded in mice bearing human papilloma viruses 16-associated TC-1 carcinoma (TU-MDSC). Although both CY-MDSC and TU-MDSC accelerated growth of TC-1 tumors in vivo, their phenotype and immunosuppressive function differed. CY-MDSC consisted of higher percentage of monocyte-like subpopulation and this was accompanied by lower relative expression of immunosuppressive genes and lower suppression of T-cell proliferation. After interferon-γ stimulation, the expression of immunosuppressive genes increased, but the suppressive ability of CY-MDSC did not reach that of TU-MDSC. The phenotype and function of MDSC obtained from mice bearing TC-1 tumors treated with CY was, in general, found to lie between CY-MDSC and TU-MDSC. After in vitro cultivation of MDSC in the presence of interleukin 12 (IL-12), the percentage of CD11b+/Gr-1+ cells decreased and was accompanied by an increase in the percentage of CD86+/MHCII+ cells. The strongest modulatory effect was noticed in the group of CY-MDSC. The susceptibility of CY-MDSC to all-trans-retinoic acid (ATRA) was also evaluated. In vitro cultivation with ATRA resulted in MDSC differentiation, and ATRA inhibited MDSC accumulation induced by CY administration. Our findings identified differences between CY-MDSC and TU-MDSC and supported the rationale for utilization of ATRA or IL-12 to alter MDSC accumulation after CY chemotherapy with the aim to improve its antitumor effect.
- MeSH
- aktivace lymfocytů MeSH
- antigeny CD11b biosyntéza imunologie MeSH
- antigeny CD86 biosyntéza imunologie MeSH
- buněčná diferenciace účinky léků MeSH
- cyklofosfamid farmakologie MeSH
- experimentální nádory imunologie patologie virologie MeSH
- interferon gama farmakologie MeSH
- interleukin-12 farmakologie MeSH
- lidé MeSH
- lidský papilomavirus 16 imunologie MeSH
- myeloidní buňky účinky léků imunologie patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie MeSH
- regulace genové exprese u nádorů MeSH
- slezina účinky léků imunologie patologie MeSH
- T-lymfocyty účinky léků imunologie patologie MeSH
- transplantace nádorů MeSH
- tretinoin farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Expresia TREM-1 receptora sa zvyšuje na povrchu myeloidných buniek v prítomnosti extracelulárnych mikroorganizmov a ich produktov. Podľa najnovších štúdií z roku 2011 sú jedným z možných etiologických agens plesne, patriace medzi extracelulárne mikroorganizmy zvyšujúce expresiu TREM-1 na povrchu buniek. V práci sme zisťovali expresie TREM-1 na povrchu myeloidných buniek a hladiny solubilnej molekuly TREM-1 (sTREM-1) v tekutine z bronchoalveolárnej laváže (BAT) pacientov s pľúcnou sarkoidózou. Zaznamenali sme zvýšené expresie TREM-1 ako aj zvýšené hladiny sTREM-1 v BAT u pacientov s pľúcnou formou sarkoidózy. Tieto výsledky poukazujú na účasť tohto receptora v imunopatogenéze pľúcnej sarkoidózy. Naše výsledky nepriamo podporujú názory autorov najnovších štúdií – účasť extraceluleárnych mikroorganizmov v etiológii sarkoidózy.
Expression of the TREM-1 receptor increases on myeloid cell surfaces in the presence of extracellular microorganisms and their products. According to the latest (2011) studies, the potential etiological agents may include fungi, extracellular microorganisms increasing TREM-1 expression on cellular surfaces. The study aimed at detecting TREM-1 expression on myeloid cell surfaces and levels of a soluble molecule of TREM-1 (sTREM-1) in bronchoalveolar lavage fluid (BALf) of patients with pulmonary sarcoidosis. Increases in both TREM-1 expression and sTREM-1 levels in BALf of patients with pulmonary sarcoidosis were observed. The ggestive of the role of this receptor in the immunopathogenesis of pulmonary sarcoidosis. They indirectly support opinions of authors of the latest studies - a role of extracellular microorganisms in the etiology of sarcoidosis.
- MeSH
- aktivace makrofágů imunologie MeSH
- aktivace neutrofilů imunologie MeSH
- biologické markery analýza MeSH
- bronchoalveolární laváž MeSH
- lidé MeSH
- membránové glykoproteiny * analýza imunologie MeSH
- myeloidní buňky cytologie fyziologie imunologie MeSH
- neutrofily imunologie MeSH
- plicní sarkoidóza * etiologie imunologie MeSH
- receptory imunologické * analýza fyziologie MeSH
- statistika jako téma MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- tabulky MeSH
