T regulatory cells are markers of disease activity in multiple sclerosis patients

FoxP3+ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS), an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis

Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumor infiltrated lymph nodes of melanoma patients

An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype and functions of NK cells from tumor-infiltrated (TILN) and tumor-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56dimCD57dimCD69+CCR7+KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared to healthy subjects, and blood NK cells also express the receptors for CCL2 and IL6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset

The mediterranean sea we want

open58siThis paper presents major gaps and challenges for implementing the UN Decade of Ocean Science for Sustainable Development (2021-2030) in the Mediterranean region. The authors make recommendations on the scientific knowledge needs and co-design actions identified during two consultations, part of the Decade preparatory-phase, framing them in the Mediterranean Sea’s unique environmental and socio-economic perspectives. According to the ‘Mediterranean State of the Environment and Development Report 2020’ by the United Nations Environment Programme Mediterranean Action Plan and despite notable progress, the Mediterranean region is not on track to achieve and fully implement the Sustainable Development Goals of Agenda 2030. Key factors are the cumulative effect of multiple human-induced pressures that threaten the ecosystem resources and services in the global change scenario. The basin, identified as a climate change vulnerability hotspot, is exposed to pollution and rising impacts of climate change. This affects mainly the coastal zones, at increasing risk of extreme events and their negative effects of unsustainable management of key economic assets. Transitioning to a sustainable blue economy is the key for the marine environment’s health and the nourishment of future generations. This challenging context, offering the opportunity of enhancing the knowledge to define science-based measures as well as narrowing the gaps between the Northen and Southern shores, calls for a joint (re)action. The paper reviews the state of the art of Mediterranean Sea science knowledge, sets of trends, capacity development needs, specific challenges, and recommendations for each Decade’s societal outcome. In the conclusions, the proposal for a Mediterranean regional programme in the framework of the Ocean Decade is addressed. The core objective relies on integrating and improving the existing ocean-knowledge, Ocean Literacy, and ocean observing capacities building on international cooperation to reach the “Mediterranean Sea that we want”.openCappelletto M.; Santoleri R.; Evangelista L.; Galgani F.; Garces E.; Giorgetti A.; Fava F.; Herut B.; Hilmi K.; Kholeif S.; Lorito S.; Sammari C.; Lianos M.C.; Celussi M.; D'alelio D.; Francocci F.; Giorgi G.; Canu D.M.; Organelli E.; Pomaro A.; Sannino G.; Segou M.; Simoncelli S.; Babeyko A.; Barbanti A.; Chang-Seng D.; Cardin V.; Casotti R.; Drago A.; Asmi S.E.; Eparkhina D.; Fichaut M.; Hema T.; Procaccini G.; Santoro F.; Scoullos M.; Solidoro C.; Trincardi F.; Tunesi L.; Umgiesser G.; Zingone A.; Ballerini T.; Chaffai A.; Coppini G.; Gruber S.; Knezevic J.; Leone G.; Penca J.; Pinardi N.; Petihakis G.; Rio M.-H.; Said M.; Siokouros Z.; Srour A.; Snoussi M.; Tintore J.; Vassilopoulou V.; Zavatarelli M.Cappelletto M.; Santoleri R.; Evangelista L.; Galgani F.; Garces E.; Giorgetti A.; Fava F.; Herut B.; Hilmi K.; Kholeif S.; Lorito S.; Sammari C.; Lianos M.C.; Celussi M.; D'alelio D.; Francocci F.; Giorgi G.; Canu D.M.; Organelli E.; Pomaro A.; Sannino G.; Segou M.; Simoncelli S.; Babeyko A.; Barbanti A.; Chang-Seng D.; Cardin V.; Casotti R.; Drago A.; Asmi S.E.; Eparkhina D.; Fichaut M.; Hema T.; Procaccini G.; Santoro F.; Scoullos M.; Solidoro C.; Trincardi F.; Tunesi L.; Umgiesser G.; Zingone A.; Ballerini T.; Chaffai A.; Coppini G.; Gruber S.; Knezevic J.; Leone G.; Penca J.; Pinardi N.; Petihakis G.; Rio M.-H.; Said M.; Siokouros Z.; Srour A.; Snoussi M.; Tintore J.; Vassilopoulou V.; Zavatarelli M

T Regulatory Cells Are Markers of Disease Activity in Multiple Sclerosis Patients

FoxP3+ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS), an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis

Transendothelial Migratory Pathways of Vδ1+TCRγδ+ and Vδ2+TCRγδ+ T Lymphocytes from Healthy Donors and Multiple Sclerosis Patients: Involvement of Phosphatidylinositol 3 Kinase and Calcium Calmodulin-Dependent Kinase II

AbstractWe have previously reported that the Vδ2+TCRγδ+ T lymphocyte subset, expressing the NK receptor protein 1a (NKRP1a; CD161), is expanded in patients with relapsing-remitting multiple sclerosis and uses this molecule to migrate through endothelium. In this work, we show that Vδ1+ and Vδ2+ γδ T lymphocytes use distinct signal transduction pathways to accomplish this function. Indeed, we have found that Vδ1+ cells lack NKRP1a and selectively express the platelet endothelial cell adhesion molecule 1 (PECAM1; CD31), which drives transendothelial migration of this cell subset, at variance with Vδ2+ T cells, which are PECAM1 negative and use NKRP1a for transmigration. Interestingly, when Vδ2+ T cells were pretreated with two specific inhibitors of the calcium calmodulin-dependent kinase II KN62 and KN93, but not with the inactive compound KN92, the number of migrating cells and the rate of transmigration were significantly decreased. In turn, the phosphatidylinositol 3 kinase blockers wortmannin and LY294002 exerted a dose-dependent inhibition of Vδ1+ cell migration. Finally, NKRP1a and PECAM1 engagement led to activation of different signal transduction pathways: indeed, oligomerization of NKRP1a on Vδ2+ T cells activates calcium calmodulin-dependent kinase II, while occupancy of PECAM1 on Vδ1+ cells triggers the phosphatidylinositol 3 kinase-dependent Akt/protein kinase Bα activation. These findings suggest that subsets of γδ T lymphocytes may migrate to the site of lesion in multiple sclerosis using two different signaling pathways to extravasate

Enrichment of KIR+CD57+ highly cytotoxic NK cells in sentinel lymph nodes of melanoma patients

Background\ud NK cells contribute to melanoma cell recognition and anti-tumor immunity, which is traditionally analyzed using human peripheral blood NK cells. An important checkpoint in the progression of malignant melanoma is the metastasis to lymph nodes.\ud \ud Materials and methods\ud To investigate the role of lymph node NK cells in disease progression, we analyzed frequency, phenotype and functions of NK cells purified from either tumor infiltrated lymph nodes or tumor-free ipsilateral lymph nodes of the same patients. Lymph node NK cells were compared to peripheral blood NK cells from either melanoma patients or healthy donors.\ud \ud Results\ud The data showed an expansion of CD56dimCD57+CD69+CCR7+KIR+ NK cells in tumor infiltrated lymph nodes. This phenotype corresponds to a recently described fully mature and highly cytotoxic NK cell population, and indeed we found that these lymph node NK cells displayed robust anti-tumor activity against autologous melanoma cells. The NK cells trafficking from periphery to the tumor draining lymph nodes have been investigated and the chemokines pattern identified. Moreover, the presence of a high proportion of KIR+CD57+CD56dim in the infiltrated lymph nodes was associated with an improved patients’ survival.\ud \ud Conclusions\ud Our data suggest that NK cells from tumor infiltrated lymph nodes are attractive candidates to improve current NK cell-based immunotherapy of melanoma