Sriram Narayanan

Agency for Science, Technology and Research (A*STAR) | A*Star · Institute of Molecular and Cell Biology (IMCB)

Objectives: Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of systemic lupus erythematosus (SLE). Despite evidence showing the importance of platelet neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of...

Objective: To study whether multimodal brain magnetic resonance imaging (MRI) comprising permeability and perfusion measures coupled with machine learning could predict neurocognitive function in young patients with systemic lupus erythematosus (SLE) without neuropsychiatric manifestation. Methods: SLE patients and healthy controls (HCs) (age ≤...

Severe mosquito bite allergy (SMBA) is a manifestation of chronic active Epstein-Barr virus (CAEBV) infection defined by necrotic ulceration of the stings. CAEBV with SMBA has a high mortality rate as most patients eventually develop fulminant and refractory hemophagocytic lymphohistiocytosis (HLH). However, how self-resolving SMBA escalates to sys...

Background Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell‐produced IL‐4 and IL‐13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B...

Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that can affect the central nervous system. Cognitive dysfuncion is the most common neuropsyhiatric event in SLE patients, yet it is also one of the hardest to diagnose. Objectives To investigate if multimodal imaging to assess anatomical magnetic resonance imaging...

Hepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis B (CHB) patients. However, the immune-pathological biomarkers and underlying mechanisms remain unclear. Here we present a comprehensive single cell-transcriptomic atlas together with immune-phenotyping of disease-a...

Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss...

Natural killer (NK) cells are innate effectors, which play a crucial role in controlling viral infections. Administration of IFN-α has shown promising results as a therapeutic, controlling HIV, and chronic viral hepatitis. However the downstream mechanisms by which IFN-α mediates its anti-viral effects is largely unknown. In this investigation, we...

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease and cystic fibrosis however its presence, frequency and clinical significance in non-CF bronchiectasis remain unclear. Objective: To determine the frequency and geographic variability that exists in sensitization pattern t...

Immunoglobulin E (IgE) is central in allergy pathology as it binds high-affinity receptors on mast cells, inducing degranulation upon allergen crosslinking. However, IgE has the lowest serum concentration and shortest half-life of all Ig’s, and IgE+ B cells are extremely rare. This work aims to uncover characteristics of IgE+B cells that could be u...

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy...

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to si...

Single-cell analysis technologies such as mass cytometry allow for measurements of cellular heterogeneity with unprecedented dimensionality. Here, we applied dimensionality reduction and automated clustering methods on human T helper (TH) cells derived from peripheral blood and tonsils, which showed differential cell composition and extensive TH ce...

The generation of long-lived plasma cells and memory B cells producing high-affinity antibodies depends on the maturation of B cell responses in germinal centers. These processes are essential for long-lasting antibody-mediated protection against infections. IgE antibodies are important for defense against parasites and toxins and can also mediate...

The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for th...

We find that the cell surface receptor Toso is dramatically downregulated by in vitro stimulation of human T and NK cells with IL-2 in a STAT5-dependent manner. The fact that IL-2 is known to prime NK and T cells for Fas/TNF-mediated activation-induced cell death (AICD) fits nicely with the original and recent descriptions of Toso as an inhibitor o...

Natural-killer (NK) cells are inflammatory cytokine-producing and/or cytotoxic lymphocytes that comprise a major component of the innate immune system. NK cells express a large variety of activating receptors dedicated to accomplishing this task, one of which is NKG2D. This receptor is also expressed on subsets of T cells, where it functions to tra...

Human naïve CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a(+) or CD300a(-). This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-gamma producing CD4 T cells showed...

Fc receptors (FcRs) are key regulators of the immune response. A receptor specific for IgM (FcμR) has been recently identified and shown to be predominately expressed on human B cells. FcμR, known previously as TOSO and as Fas apoptosis inhibitory molecule 3 (Faim3), has no role in the inhibition of Fas-mediated apoptosis. We have examined the expr...

ITIM-containing receptors play an essential role in modulating immune responses. Leukocyte-associated inhibitory receptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all leukocytes, that binds collagens. In this article, we investigate the effect of a conservative R65K mutation on LAIR-1 ligand binding and...

Homeostasis of both NK and T cells in the periphery is regulated by activation induced cell death (AICD) mediated by signaling through Fas, and other death receptors. It has been shown that IL-2 is required for priming cells for this type of apoptosis. Cytokine primed NK cells, in addition to killing their target cells, also undergo AICD upon activ...

Regulated apoptosis is essential for both the development and homeostasis of the immune system. Fas-mediated cell death has been implicated in apoptosis during the development and homeostasis of lymphocytes, and this apoptosis pathway is regulated by the interplay of BCL-2-family members, as well as other factors, such as cytokine withdrawal. Howev...

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated Fcvar...

The CD94/NKG2A inhibitory receptor, expressed by natural killer and T cells, is constantly exposed to its HLA-E ligand expressed by surrounding cells. Ligand exposure often induces receptor downregulation. For CD94/NKG2A, this could potentiate activation receptor(s) induced responses to normal bystander cells. We investigated CD94/NKG2A endocytosis...

NK cells are critical components of our immune system functioning, in part, to recognize and then eradicate virally infected or tumorigenic cells without previous sensitization. One of the best-characterized activating receptors expressed on NK cells is the NKG2D receptor, which is capable of transmitting co-stimulatory signals by subsets of T cell...

Human leukocyte-associated Ig-like receptor-1 (LAIR-1) is an immunoreceptor tyrosine based inhibitory motif (ITIM) containing inhibitory receptor that is expressed on the majority of PBMCs and thymocytes. The ligand for LAIR-1 has recently been identified as collagens. Since collagens represent the most abundant type of proteins in vertebrates it i...

Ribosome inactivating proteins (RIPs) are protein toxins that are of plant or microbial origin that inhibit protein synthesis by inactivating ribosomes. Recent studies suggest that RIPs are also capable of inducing cell death by apoptosis. Though many reports are available on cell death induced by RIPs, the mechanism involved is not well studied. C...

Ribosome inactivating proteins (RIPs) are protein toxins that are of plant or microbial origin that inhibit protein synthesis by inactivating ribosomes. Recent studies suggest that RIPs are also capable of inducing cell death by apoptosis. Though many reports are available on cell death induced by RIPs, the mechanism involved is not well studied. C...

Abrin belongs to the type II family of ribosome-inactivating proteins comprising a galactose-binding B chain coupled with a toxic A chain through a single disulphide linkage. Apart from its RNA-N-glycosidase activity, another role that has been recently ascribed to abrin was the induction of apoptosis. Studies were undertaken to determine the kinet...

The eye lens small heat shock proteins (sHSP), alphaA- and alphaB-crystallins, have been shown to function like molecular chaperones, both in vitro and in vivo. It is essential to assess the protective effect of alphaA- and alphaB-crystallins under native conditions to extrapolate the results to in vivo conditions. Insulin and alpha-lactalbumin hav...

The eye lens small heat shock proteins (sHSP), αA- and αB-crystallins, have been shown to function like molecular chaperones, both in vitro and in vivo. It is essential to assess the protective effect of αA- and αB-crystallins under native conditions to extrapolate the results to in vivo conditions. Insulin and α-lactalbumin have widely been used t...