The fetal immune system is distinguishable from the adult immune system by a higher degree of tolerance to foreign antigens. This tolerance is important for fetal development within the 'foreign' maternal environment, and during birth when barrier surfaces are first colonized by microbiota. Immune responses against the wave of newly colonizing microbiota would cause massive damage to barrier tissues, so neonates need suppressed immune responses and instead rely on maternal antibodies for protect...
Multiple Sclerosis (MS) is currently thought to arise by interactions between genetic susceptibility and environmental factors. Infections in general trigger autoimmune responses causing clinical manifestations of disease. However, as a result of regulatory T (Treg) and regulatory B (Breg) cell induction, helminth-infections tend to dampen disease activity. IL-35, the newest member of the IL-12 family, is a inhibitory cytokine composed of an EBI3β chain subunit, and an IL-12p35 subunit. The aim ...
#1Marianne Strazza(CUMC: Columbia University Medical Center)H-Index: 3
#2Shoiab Bukhari(CUMC: Columbia University Medical Center)H-Index: 7
Last. Adam Mor(CUMC: Columbia University Medical Center)H-Index: 4
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Ligation of the inhibitory receptor PD-1 on T cells results in the inhibition of numerous cellular functions. Despite the overtly inhibitory outcome of PD-1 signalling, there are additionally a collection of functions that are activated. We have observed that CD4+ T cells stimulated through the T-cell receptor and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than T-cell receptor stimulation alone. These highly proliferating cells could potenti...
IL-33 and ATP are alarmines which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high density expression of the IL-33 receptor T1/ST2 (IL-33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL-33 or ATP in damaged peripheral tissues. Whereas IL-33 induces the MyD88-dependent activation of the TAK1-IKK2-NF-κB signaling, ATP induces the Ca2+ -dependent activation of NFAT. Thereby eac...
Last. Muazzam Jacobs(National Health Laboratory Service)H-Index: 30
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Tuberculosis presents a global health challenge and tumor necrosis factor (TNF) signaling is required for host immunity against Mycobacterium tuberculosis (Mtb). TNF receptor shedding however compromises effective immunity by reducing bioactive TNF through the formation of inactive complexes. In this study, we first compared the effect of total soluble TNF receptors using a transgenic p55ΔNS /p75-/- murine strain on host protection during a low-dose aerosol Mtb H37Rv challenge. We report that th...
A number of mechanisms have been proposed to explain the well-established link between diabetic status and an increase susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID-19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here we point out key findings implicating dysregulated insu...
Loss of the B2M gene is associated with tumor immune escape and resistance to immunotherapy. However, genetic alterations of the B2M gene are rare. We performed an integrative analysis of the mutational and transcriptional profiles of large cohorts of non-small-cell lung cancer (NSCLC) patients and found that epigenetic downregulation of B2M is common. B2M-low tumors exhibit a suppressive immune microenvironment characterized by reduced infiltration of immune cells of various lineages; in B2M-hi...
Last. Ferry Ossendorp(LUMC: Leiden University Medical Center)H-Index: 66
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An exclusive feature of dendritic cells (DCs) is their capacity to present exogenous antigens by MHC class I molecules, called cross-presentation. Here we show that protein antigen can be conserved in mature murine DCs for several days in a lysosome-like storage compartment, distinct from MHC class II and early endosomal compartments, as an internal source for the supply of MHC class I ligands. Using two different uptake routes via Fcγ receptors and C-type lectin receptors, we could show that an...
Last. Xiao-jie He(CSU: Central South University)H-Index: 5
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Plasmacytoid dendritic cells (pDCs) play a key role in the initiation and amplification of systemic lupus erythematosus (SLE)-associated vascular injury. In this study, we found that dsDNA induced dose and time-dependent increase in IFN-α and toll-like receptor 7 (TLR7), TLR9 and IRF7 expression in pDCs. Co-cultured circulating endothelial cells (ECs) with activated pDCs significantly decreased proliferation, tube formation and migration in ECs. The elevated level of cellular IFN-α increased cel...
#1Simon Milling(Glas.: University of Glasgow)H-Index: 27
The immune system must be tightly controlled to prevent potentially damaging over-response to pathogens and must also be actively maintained in a responsive state when no immediate threat is present. These processes of control and maintenance are important for sustaining a state of immune homeostasis and are controlled by a network of cellular and molecular interactions. Here, we highlight a recent publication in Immunology (2021) where the authors have examined the effects of the thyroid and pi...