Increased Expression of sST2 in Early HIV Infected Patients Attenuated the IL-33 Induced T Cell Responses

Abstract

T cell responses were less functional and persisted in an exhausted state in chronic HIV infection. Even in early phase of HIV infection, the dysfunction of HIV-specific T cells can be observed in rapid progressors, but the underlying mechanisms are not fully understood. Cytokines play a central role in regulating T cell function. In this study, we sought to elucidate whether IL-33/ST2 axis plays roles in the regulation of T cell function in HIV infection. We found that the level of IL-33 was upregulated in early HIV-infected patients compared with that in healthy controls and has a trend associated with disease progression. In vitro study shows that IL-33 promotes the expression of IFN-γ by Gag stimulated CD4+ and CD8+T cells from HIV-infected patients to a certain extent. However, soluble ST2 (sST2), a decoy receptor of IL-33, was also increased in early HIV infected patients, especially in those with progressive infection. We found that anti-ST2 antibodies attenuated the effect of IL-33 to CD4+ and CD8+T cells. Our data indicates that elevated expression of IL-33 in early HIV infection has the potential to enhance the function of T cells, but the upregulated sST2 weakens the activity of IL-33, which may indirectly contribute to the dysfunction of T cells and rapid disease progression. This data broadens the understanding of HIV pathogenesis and provides critical information for HIV intervention.

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

“…The NLRP3 gene is located on the long arm of chromosome 1q44 and reacts to a diverse set of endogenous or exogenous stimuli [63]. NLRP3 has been linked to the pathogenesis of several diseases, including [1] metabolic disorders, such as type 2 diabetes [64], obesity [65], and autoimmune and inflammatory diseases [66][67][68]; neurological diseases [69]; and [2] diseases caused by viral pathogens, such as HIV [50], influenza A [70], and SARS-CoV [71]. SNPs in the NLRP3 gene have already been associated with a group of inflammatory disorders of genetic origin [32,72].…”

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

“…Current research has established some pathological mechanisms that are related to IRIS development, such as high viral loads, low baseline CD4+ T-cell counts (<50-100 cells/mm3) (Antonelli et al, 2010;Luetkemeyer et al, 2014) with high levels of CD4 activation and replication (Tibuŕcio et al, 2021), and short time intervals between TB treatment and cART (French et al, 2004;Chang et al, 2014;Tan et al, 2016). The genetic basis of host susceptibility to infectious diseases has received enormous attention (Fellay et al, 2009;Seaby et al, 2016;Wu et al, 2017). Highly polymorphic class I and II human leukocyte antigens (HLAs), killer-cell immunoglobulin-like receptor (KIR), cytokine genes, and genes involved in inflammation (inflammasome genes) are actively contributing factors that are associated with susceptibility and/or resistance to TB and HIV-1 infection (Kulkarni et al, 2008;Levy, 2009;Martin and Carrington, 2013;Pontillo et al, 2013;De Lima et al, 2016;Naranbhai and Carrington, 2017;Tsiara et al, 2018;de Sáet al, 2020).…”

LncRNA ANRIL knockdown relieves myocardial cell apoptosis in acute myocardial infarction by regulating IL-33/ST2

“…In terms of novel aspects of this study, no other studies have investigated the role of lncRNA ANRIL in affecting the degradation of IL-33 in myocardial cells, which will enrich the literature and shed light on the underlying mechanism of lncRNA ANRIL in myocardial cell apoptosis after AMI. Numerous studies have shown that IL-33 could exert its functions by targeting ST2 in immune response or cancers [23,24]. IL-33 can recognize and interact with its specific receptor ST2 in immune cells, and anti-ST2 antibody reduced the effect of IL-33 on CD4 + T and CD8 + T cells during HIV-1 infection [23].…”

“…Numerous studies have shown that IL-33 could exert its functions by targeting ST2 in immune response or cancers [23,24]. IL-33 can recognize and interact with its specific receptor ST2 in immune cells, and anti-ST2 antibody reduced the effect of IL-33 on CD4 + T and CD8 + T cells during HIV-1 infection [23]. IL-33/ST2 axis was involved in the activity of mast cells during colitis, and IL-33 promoted the percentage of IL-13/IL-22 producing T cells, which indicated that IL-33 regulated T cell differentiation and function [24].…”