IL-21/23 axis modulates inflammatory cytokines and RANKL expression in RA CD4 T cells via p-Akt1 signaling.

Introduction: CD4 T cells are critically involved in the pathogenesis of Rheumatoid Arthritis; an autoimmune disorder characterized by joint inflammation and bone degeneration. In this study, we focused on the critical role of cytokines, IL-21 and IL-23 in facilitating the aberrant status of RA Th17-like cells and report their significant contribution(s) in modulating the expression of inflammatory cytokines and RANKL.

Methods: Blood and synovial fluid collected from a total of 167 RA patients and 25 healthy volunteers were assessed for various inflammatory markers and RANKL expression in plasma and CD4 T cells.

Perturbations in spike-specific peripheral T follicular helper cells in SARS-CoV2 breakthrough convalescent individuals immunized by BBV152 vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection has caused an increase in mortality and morbidity, but with vaccination, the disease severity has significantly reduced. With the emergence of various variants of concern (VOCs), the vaccine breakthrough infection has also increased. Here we studied circulating spike-specific T follicular response (cTfh) in infection-naïve vaccinees and convalescent vaccinees (individuals who got the Delta breakthrough infection after two doses of BBV152 vaccine) to understand their response as they are the most crucial cells that are involved in vaccine-mediated protection by helping in B-cell maturation.

IL-21, Inflammatory Cytokines and Hyperpolarized CD8 T Cells Are Central Players in Lupus Immune Pathology.

Systemic lupus erythematous (SLE) is a chronic autoimmune disorder, broadly characterized by systemic inflammation along with heterogeneous clinical manifestations, severe morbidity, moribund organ failure and eventual mortality. In our study, SLE patients displayed a higher percentage of activated, inflamed and hyper-polarized CD8 T cells, dysregulated CD8 T cell differentiation, significantly elevated serum inflammatory cytokines and higher accumulation of cellular ROS when compared to healthy controls. Importantly, these hyper-inflammatory/hyper-polarized CD8 T cells responded better to an antioxidant than to an oxidant.

Underlying Co-Morbidity Reveals Unique Immune Signatures in Type II Diabetes Patients Infected With SARS-CoV2.

Background: SARS-CoV2 infection in patients with comorbidities, particularly T2DM, has been a major challenge globally and has been shown to be associated with high morbidity and mortality. Here, we did whole blood immunophenotyping along with plasma cytokine, chemokine, antibody isotyping, and viral load from oropharyngeal swab to understand the immune pathology in the T2DM patients infected with SARS-CoV2.

Methods: Blood samples from 25 Covid-19 positive patients having T2DM, 10 Covid-19 positive patients not having T2DM, and 10 Covid-19 negative, non-diabetic healthy controls were assessed for various immune cells by analyzing for their signature surface proteins in mass cytometry.

iCa Flux, ROS and IL-10 Determines Cytotoxic, and Suppressor T Cell Functions in Chronic Human Viral Infections.

Exhaustion of CD8 T cells and increased IL-10 production is well-known in chronic viral infections but mechanisms leading to loss of their cytotoxic capabilities and consequent exhaustion remain unclear. Exhausted CD8T cells also called T suppressors are highly immune suppressive with altered T cell receptor signaling characteristics that mark it exclusively from their cytotoxic counterparts. Our study found that iCa flux is reduced following T cell receptor activation in T suppressor cells when compared to their effector counterpart.

Inducible Costimulator Expressing T Cells Promote Parasitic Growth During Blood Stage ANKA Infection.

The lethality of blood stage (PbA) infection is associated with the expression of T-bet and production of cytokine IFN-γ. Expression of inducible costimulator (ICOS) and its downstream signaling has been shown to play a critical role in the T-bet expression and IFN-γ production. Although earlier studies have examined the role of ICOS in the control of acute blood-stage infection of AS (a non-lethal model of malaria infection), its significance in the lethal blood-stage of PbA infection remains unclear.

Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.

Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4 T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet.