IL-3 regulates the differentiation of pathogenic Th17 cells.

IL-17-producing Th17 cells play an important role in pathogenesis of rheumatoid arthritis (RA). Aberrant immune activation due to an imbalance between Th17 and regulatory T (Treg) cells is associated with the development of RA and other autoimmune diseases. Targeting pathogenic Th17 cells and their associated molecules is emerging as a promising strategy to treat and reverse RA.

Regulatory B Cells (Bregs) Inhibit Osteoclastogenesis and Play a Potential Role in Ameliorating Ovariectomy-Induced Bone Loss.

Increasing evidence in recent years has suggested that regulatory B cells (Bregs) are one of the crucial modulators in various inflammatory disease conditions. However, no study to date has investigated the significance of Bregs in modulating osteoclastogenesis. To the best of our knowledge, in the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under conditions and observed that Bregs suppress RANKL-induced osteoclastogenesis in a dose-dependent manner.

COVID-19: Immunology, Immunopathogenesis and Potential Therapies.

The Coronavirus Disease-2019 (COVID-19) imposed public health emergency and affected millions of people around the globe. As of January 2021, 100 million confirmed cases of COVID-19 along with more than 2 million deaths were reported worldwide. SARS-CoV-2 infection causes excessive production of pro-inflammatory cytokines thereby leading to the development of "Cytokine Storm Syndrome.

IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL-4, and IL-3 Synergizes with IL-4 to Enhance Th2 Cell Differentiation.

IL-3, a cytokine secreted by activated T lymphocytes, is known to regulate the proliferation, survival, and differentiation of hematopoietic cells. However, the role of IL-3 in regulation of T cell functions is not fully delineated. Previously, we have reported that IL-3 plays an important role in development of regulatory T cells in mice.

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction.

TLR9-deficiency reduces TLR1, TLR2 and TLR3 expressions in Leishmania major-infected macrophages.

The parasite Leishmania major counteractively modulates TLR2 and TLR9 expression and their functions. Although TLR1, TLR3, TLR4, and TLR7 are also implicated in Leishmania infection, whether their expression was altered in TLR2 or TLR9 deficiency remained unknown. Therefore, we examined TLR1, TLR3, TLR4 and TLR7 expression in L.

IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells.

IL-3 is an important cytokine that regulates hematopoiesis. We have previously demonstrated that IL-3 is a potent inhibitor of osteoclastogenesis and bone resorption. In the present study, we have investigated the role of IL-3 on human osteoblast differentiation and bone formation.

IL-3 attenuates collagen-induced arthritis by modulating the development of Foxp3+ regulatory T cells.

IL-3, a cytokine secreted by Th cells, functions as a link between the immune and the hematopoietic system. We previously demonstrated the potent inhibitory role of IL-3 on osteoclastogenesis, pathological bone resorption, and inflammatory arthritis. In this study, we investigated the novel role of IL-3 in development of regulatory T (Treg) cells.

IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage.

IL-3 is an important cytokine that regulates hematopoiesis and functions as a link between the immune and the hematopoietic system. In this study, we investigated the role and mechanism of IL-3 action on human osteoclast formation and bone resorption using PBMCs. PBMCs differentiate into functional osteoclasts in the presence of M-CSF and receptor activator of NF-kappaB ligand as evaluated by 23c6 expression and bone resorption.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine.

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs.

IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India.

Background: The main processes in the pathogenesis of cerebral malaria caused by Plasmodium falciparum involved sequestration of parasitized red blood cells and immunopathological responses. Among immune factors, IgG autoantibodies to brain antigens are increased in P. falciparum infected patients and correlate with disease severity in African children.

Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat accumulation and upregulation of LDL receptor.

Fenugreek (Trigonella foenum-graecum) seeds, used as a condiment, are documented for health benefits including amelioration of abnormalities in lipid homeostasis due to its hypolipidemic properties. However, molecular mechanisms underlying the hypolipidemic effect of fenugreek seeds remain obscure. In this study, hypolipidemic effect of a novel thermostable extract of fenugreek seeds (TEFS) was evaluated in vitro by employing differentiating and differentiated 3T3-L1 cells, and HepG2 cells cultured in normal or sterol-enriched conditions.

IL-3 inhibits TNF-alpha-induced bone resorption and prevents inflammatory arthritis.

IL-3, a cytokine secreted by activated T cells is well known to regulate the proliferation, differentiation, and survival of pluripotent hematopoietic stem cells. IL-3 functions as a link between the immune and the hematopoietic system. In this study, we suggest an important new role of IL-3 in inhibition of TNF-alpha-induced bone resorption in vitro and prevention of inflammatory arthritis in mice.

Interleukin-12 is necessary for the priming of CD4+ T cells required during the elicitation of HIV-1 gp120-specific cytotoxic T-lymphocyte function.

The mechanism of the T-cell response and cytokine induction to restrict human immunodeficiency virus 1 (HIV-1) infection is not clear. During early infection, HIV-infected individuals have a high frequency of virus-specific cytotoxic T lymphocytes (CTLs) that effectively reduces the viral load. However, the CTLs are unable to clear the virus at later stages of infection, leading to disease progression.

HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner.

A large number of multicomponent vaccine candidates are currently in clinical evaluation, many of which also include the HIV-1 Tat protein, an important regulatory protein of the virus. However, whether Tat, a known immune effector molecule with a well-conserved sequence among different HIV subtypes, affects the immune response to a coimmunogen is not well understood. In this study, using a bicistronic vector expressing both gp120 and Tat, we have analyzed the role of Tat in elicitation of the gp120-specific immune response.

Differential CD40/CD40L expression results in counteracting antitumor immune responses.

Establishment of host-protective memory T cells against tumors is the objective of an antitumor immunoprophylactic strategy such as reinforcing T cell costimulation via CD40-CD40L interaction. Previous CD40-targeted strategies assumed that T cell costimulation is an all-or-none phenomenon. It was unknown whether different levels of CD40L expression induce quantitatively and qualitatively different effector T cell responses.

Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status.

Background: There is an increase of serum levels of IgE during Plasmodium falciparum infections in individuals living in endemic areas. These IgEs either protect against malaria or increase malaria pathogenesis. To get an insight into the exact role played by IgE in the outcome of P.

Functional dichotomy in CD40 reciprocally regulates effector T cell functions.

Activation of T cells requires signals through Ag-specific TCR and costimulatory molecules such as CD40L. Although the use of defined tumor Ags for the induction of protective T cells met with limited success, the CD40-CD40L interaction that was proposed to induce antitumor T cells did not prevent tumor growth completely. Using a model for prostate tumor, a leading cause of tumor-induced mortality in men, we show that the failure is due to a novel functional dichotomy of CD40 whereby it self-limits its antitumor functions by inducing IL-10.

Clusters of cytokines determine malaria severity in Plasmodium falciparum-infected patients from endemic areas of Central India.

We investigated the role of interferon (IFN)- gamma , interleukin (IL)-1 beta , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- alpha , and transforming growth factor (TGF)- beta in clinically well-defined groups of Plasmodium falciparum-infected patients manifesting mild malaria (MM), severe noncerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria-endemic site in India, as well as in healthy subjects from non-malaria-endemic areas. Two-way coupled cluster analysis revealed 2 clusters of cytokines relevant to clinical subgroups of disease. The first cluster was composed of IFN- gamma , IL-2, IL-5, IL-6, and IL-12, the levels of which were significantly increased during infection but were predominant in patients with MM and allowed us to distinguish them from patients with SM or CM.

Stem cell pharmacogenomics: a reality check on stem cell therapy.

Widespread applications of stem cell-based therapies in the clinic are being reported, yet there is a surprising lack of resolution of the factors that lead to failure of such therapies on a long-term basis. While classical pharmacogenomics aids the prediction of drug responses in an individual based on genetic variation and pharmacological responses, stem cell therapy involves an additional dimension of host-donor cell interactions and adaptability. We propose the development of concise guidelines based on pharmacogenetic and donor/host-related cellular factors studied more extensively in larger data sets, and used in prospective studies to individualize stem cell therapy.

B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40 antibody, induce anergy in CD8+ T cells: role of TGF-beta 1.

B cells recognize Ag through their surface IgRs and present it in the context of MHC class II molecules to CD4(+) T cells. Recent evidence indicates that B cells also present exogenous Ags in the context of MHC class I to CD8(+) T cells and thus may play an important role in the modulation of CTL responses. However, in this regard, conflicting reports are available.

Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule.

After the engagement of Ag receptor, most of the Th cells for their optimal activation require a second (costimulatory) signal provided by the APCs. We demonstrate the isolation and characterization of a 99- to 105-kDa protein (B2), from LPS-activated B cell surface, and its function as a Th2-specific costimulatory molecule. Appearance of B2 as a single entity on two-dimensional gel electrophoresis and as a distinct peak in reverse-phase HPLC ascertains the fact that B2 is homogeneous in preparation.

The Th1-specific costimulatory molecule, m150, is a posttranslational isoform of lysosome-associated membrane protein-1.

In an earlier report, we had shown a 150-kDa protein termed as M150, isolated from the surface of activated macrophages, to possess costimulatory activity for CD4(+) T cells. Significantly, this protein was found to specifically elicit Th1 responses. In this study, we characterize M150, which belongs to a unique subset of the lysosome-associated membrane protein-1 glycoprotein.