Publications by authors named "Jessica N Peel"
Article Synopsis
- T follicular helper (Tfh) cells, which are important for antibody production, rely heavily on the immunoreceptor PD-1, and its deficiency leads to weakened Tfh functions and impaired immune responses in mice.
- Individuals lacking PD-1 or PD-L1 demonstrate fewer memory B cells and diminished antibody responses, highlighting the critical role of these molecules in immune system functionality.
- PD-1 influences both the intrinsic and extrinsic aspects of B cell memory and antibody production, suggesting that disruptions in PD-1 signaling can lead to complications in immune responses, especially during anti-PD-1-PD-L1 therapies.
The prototypic IFN-inducible transcription factor, IRF1, not only controls inflammatory gene expression but also regulates T cell and macrophage fate specification and function. Using bone marrow chimeras (80% B6.129S2-Ighmtm1Cgn/J [µMT] + 20% B6.
View Article and Find Full Text PDFBACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.
View Article and Find Full Text PDFPurpose: Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Twenty-two genes with products involved in the production of, or response to, IFN-γ and variants of which underlie MSMD have been identified. However, pathogenic variants of IFNG encoding a defective IFN-γ have been described in only two siblings, who both underwent hematopoietic stem cell transplantation (HCST).
View Article and Find Full Text PDFArticle Synopsis
- * This deficiency results in the impaired translation of important proteins like JAK2, affecting cellular responses to specific cytokines such as IL-23 and IL-12, particularly in T lymphocytes and phagocytes.
- * The impaired response to IL-23 reduces the production of IFN-γ by certain immune cells during mycobacterial infections, highlighting a crucial link between MCTS1 deficiency and mycobacterial disease susceptibility.
Article Synopsis
- Inborn errors affecting the immune response to IFN-γ lead to mycobacterial diseases, while errors in IFN-α/β impact defense against viral infections.
- A study of children with complete IRF1 deficiency showed they suffered from severe mycobacterial infections but displayed normal responses to various viruses, including SARS-CoV-2.
- IRF1 plays a crucial role in the immune response to mycobacteria, enhancing IFN-γ responses, while its absence does not significantly hinder antiviral defenses associated with IFN-α/β.
Article Synopsis
- High expression of the transcription factor T-bet is linked to a unique type of B cell called "age-associated B cells" (ABCs) in mice, and T-bet deficiency can lead to fewer ABCs and weakened immune responses.
- A patient with T-bet deficiency showed normal overall immune responses but had an unusual pattern of antibody class switching and distinct B cell characteristics, similar to ABCs in mice.
- T-bet plays a crucial role in the development of a specific subset of human B cells, impacting their differentiation and genetic programming, while being less critical for maintaining long-term effective humoral immunity.
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity.
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- - The COVID-19 pandemic has highlighted the need for effective vaccinations to combat the spread of SARS-CoV-2, with a focus on intranasal vaccines as they target the nasal mucosa, the first barrier to infection.
- - Current vaccines mainly provide systemic immunity via intramuscular injection, lacking the ability to activate mucosal defenses.
- - The AdCOVID vaccine, an intranasal adenovirus-based vaccine, successfully induces strong immune responses, including mucosal IgA and T cells, making it a promising candidate for COVID-19 prevention.
Although viral infections elicit robust interferon-γ (IFN-γ) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-γR and the IFN-γ-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-γR signaling induced Blimp1 expression in B cells but also initiated an inflammatory gene program that, if not restrained, prevented ASC formation.
View Article and Find Full Text PDFDevelopment of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance.
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