Adam J. Fike
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View article: IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints
IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints Open
How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC) and autoan…
View article: miR-21 promotes B cell autoreactivity, inflammatory signaling, and metabolism in TLR7-driven systemic autoimmunity
miR-21 promotes B cell autoreactivity, inflammatory signaling, and metabolism in TLR7-driven systemic autoimmunity Open
MicroRNA-21 (miR-21) is upregulated in SLE patients and promotes disease in multiple autoimmune mouse models; however, mechanisms by which miR-21 promote autoimmunity are unknown. Here we show that TLR7 overexpressing SLE-prone B6.Sle1bYaa…
View article: STAT3 signaling in B cells controls germinal center zone organization and recycling
STAT3 signaling in B cells controls germinal center zone organization and recycling Open
Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we show a B cell-intrinsic role for signal transducer and activator of transcription 3 (STAT3) in GC DZ and LZ organiza…
View article: Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells
Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells Open
The essential role of store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling …
View article: Author response: Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells
Author response: Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Methods Appendix 1 Data availability References Decision letter Author response Article and author information Metrics Abstract The essential role of sto…
View article: Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells
Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells Open
The essential role of store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling …
View article: Context-Dependent miR-21 Regulation of TLR7-Mediated Autoimmune and Foreign Antigen–Driven Antibody-Forming Cell and Germinal Center Responses
Context-Dependent miR-21 Regulation of TLR7-Mediated Autoimmune and Foreign Antigen–Driven Antibody-Forming Cell and Germinal Center Responses Open
MicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance in systemic lupus erythematosus (SLE), although the role of many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to redu…
View article: Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses
Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses Open
MicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance in systemic lupus erythematosus (SLE), though the role of many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to reduce…
View article: STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus–like Autoimmune- and Foreign Antigen–Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses
STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus–like Autoimmune- and Foreign Antigen–Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses Open
Genome-wide association studies identified variants in the transcription factor STAT4 gene and several other genes in the STAT4 signaling pathway, such as IL12A, IL12B, JAK2, and TYK2, which are associated with an increased risk of develop…
View article: TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner Open
IL-10 producing B cells (B10 cells) play an important immunoregulatory role in various autoimmune and infection conditions. However, the factors that regulate their development and maintenance are incompletely understood. Recently, we and …
View article: The native ORAI channel trio underlies the diversity of Ca2+ signaling events
The native ORAI channel trio underlies the diversity of Ca2+ signaling events Open
The essential role of ORAI1 channels in receptor-evoked Ca 2+ signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have …
View article: Serine Phosphorylation of the STAT1 Transactivation Domain Promotes Autoreactive B Cell and Systemic Autoimmunity Development
Serine Phosphorylation of the STAT1 Transactivation Domain Promotes Autoreactive B Cell and Systemic Autoimmunity Development Open
Although STAT1 tyrosine-701 phosphorylation (designated STAT1-pY701) is indispensable for STAT1 function, the requirement for STAT1 serine-727 phosphorylation (designated STAT1-pS727) during systemic autoimmune and antipathogen responses r…
View article: Type II but Not Type I IFN Signaling Is Indispensable for TLR7-Promoted Development of Autoreactive B Cells and Systemic Autoimmunity
Type II but Not Type I IFN Signaling Is Indispensable for TLR7-Promoted Development of Autoreactive B Cells and Systemic Autoimmunity Open
TLR7 is associated with development of systemic lupus erythematosus (SLE), but the underlying mechanisms are incompletely understood. Although TLRs are known to activate type I IFN (T1IFN) signaling, the role of T1IFN and IFN-γ signaling i…
View article: Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG Open
Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old …
View article: Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses
Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses Open
Germinal centers (GCs) are essential for the production of somatically hypermutated, class-switched Abs that are protective against infection, but they also form in the absence of purposeful immunization or infection, and are termed sponta…
View article: Dissecting the defects in the neonatal CD8+ T-cell response
Dissecting the defects in the neonatal CD8+ T-cell response Open
The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8+ T cells are critical for the resp…
View article: Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production
Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production Open
The underlying mechanisms that regulate neonatal immune suppression are poorly characterized. CD31 (PECAM1) is highly expressed on neonatal lymphocytes and is a known modulator of TCR signaling. To further characterize the role of CD31 in …
View article: Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155
Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155 Open
Persistent viral infections and tumors drive development of exhausted T (TEX) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over …
View article: Public Clonotypes and Convergent Recombination Characterize the Naïve CD8+ T-Cell Receptor Repertoire of Extremely Preterm Neonates
Public Clonotypes and Convergent Recombination Characterize the Naïve CD8+ T-Cell Receptor Repertoire of Extremely Preterm Neonates Open
Respiratory support improvements have aided survival of premature neonates, but infection susceptibility remains a predominant problem. We previously reported that neonatal mice have a rapidly evolving T-cell receptor (TCR) repertoire that…
View article: The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1
The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1 Open
We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8+ T lymphocytes (CTL) generation and effector memory cell formation, is regulated in CTL by microRNA-1…
View article: Characterization of CD31 expression on murine and human neonatal T lymphocytes during development and activation
Characterization of CD31 expression on murine and human neonatal T lymphocytes during development and activation Open
View article: Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections
Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections Open
The p110δ isoform of PI3K is known to play an important role in immunity, yet its contribution to CTL responses has not been fully elucidated. Using murine p110δ-deficient CD8+ T cells, we demonstrated a critical role for the p110δ subunit…