RESUMEN
Innate immune sensing of cytosolic DNA via absent in melanoma 2 (AIM2) is a key mechanism leading to inflammatory responses. As aberrant immune responses by dysregulated AIM2 are associated with autoinflammatory diseases, activation of the AIM2 inflammasome should be tightly controlled. In this study, we discovered that ubiquitination and deubiquitination of AIM2 are critical events that regulate AIM2 inflammasome activation. In resting human macrophage cells, AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation to avoid autoinflammation. Upon DNA stimulation, USP21 binds to AIM2 and deubiquitinates it, thereby increasing its protein stability. In addition to the role of USP21 in regulating AIM2 turnover, we uncovered that USP21-mediated deubiquitination of AIM2 is required for the assembly of the AIM2 inflammasome. Depletion of USP21 does not affect the DNA-binding ability of AIM2 but inhibits the formation of the AIM2-ASC complex. Our findings establish that fine-tuning of AIM2 by the ubiquitin system is important for regulating AIM2 inflammasome activation.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Inflamasomas/metabolismo , Inflamación/inmunología , Macrófagos/inmunología , Ubiquitina Tiolesterasa/metabolismo , Regulación de la Expresión Génica , Células HEK293 , Humanos , Inmunidad Innata , Unión Proteica , Estabilidad Proteica , ARN Interferente Pequeño/genética , Células THP-1 , Ubiquitina Tiolesterasa/genética , UbiquitinaciónRESUMEN
BACKGROUND: In addition to addiction and substance abuse, motivational interviewing (MI) is increasingly being integrated in treating other clinical issues such as mental health problems. Most of the many technological adaptations of MI, however, have focused on delivering the action-oriented treatment, leaving its relational component unexplored or vaguely described. This study intended to design a conversational sequence that considers both technical and relational components of MI for a mental health concern. OBJECTIVE: This case study aimed to design a conversational sequence for a brief motivational interview to be delivered by a Web-based text messaging application (chatbot) and to investigate its conversational experience with graduate students in their coping with stress. METHODS: A brief conversational sequence was designed with varied combinations of MI skills to follow the 4 processes of MI. A Web-based text messaging application, Bonobot, was built as a research prototype to deliver the sequence in a conversation. A total of 30 full-time graduate students who self-reported stress with regard to their school life were recruited for a survey of demographic information and perceived stress and a semistructured interview. Interviews were transcribed verbatim and analyzed by Braun and Clarke's thematic method. The themes that reflect the process of, impact of, and needs for the conversational experience are reported. RESULTS: Participants had a high level of perceived stress (mean 22.5 [SD 5.0]). Our findings included the following themes: Evocative Questions and Clichéd Feedback; Self-Reflection and Potential Consolation; and Need for Information and Contextualized Feedback. Participants particularly favored the relay of evocative questions but were less satisfied with the agent-generated reflective and affirming feedback that filled in-between. Discussing the idea of change was a good means of reflecting on themselves, and some of Bonobot's encouragements related to graduate school life were appreciated. Participants suggested the conversation provide informational support, as well as more contextualized feedback. CONCLUSIONS: A conversational sequence for a brief motivational interview was presented in this case study. Participant feedback suggests sequencing questions and MI-adherent statements can facilitate a conversation for stress management, which may encourage a chance of self-reflection. More diversified sequences, along with more contextualized feedback, should follow to offer a better conversational experience and to confirm any empirical effect.
Asunto(s)
Adaptación Psicológica/fisiología , Entrevista Motivacional/métodos , Adulto , Comunicación , Retroalimentación , Femenino , Humanos , Masculino , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/enzimología , Fosfatos de Dinucleósidos/química , Proteínas de Unión al GTP Monoméricas/química , Malformaciones del Sistema Nervioso/enzimología , ARN/química , Proteínas de los Retroviridae/química , Ribonucleasas/química , Sitios de Unión , Activación Enzimática , Humanos , Hidrólisis , Fosforilación , Unión Proteica , Proteína 1 que Contiene Dominios SAM y HDRESUMEN
BACKGROUND: Human SAMHD1 possesses dual enzymatic functions. It acts as both a dGTP-dependent triphosphohydrolase and as an exoribonuclease. The dNTPase function depletes the cellular dNTP pool, which is required for retroviral reverse transcription in differentiated myeloid cells and resting CD4(+) T cells; thus this activity mainly plays a role in SAMHD1-mediated retroviral restriction. However, a recent study demonstrated that SAMHD1 directly targets HIV-1 genomic RNA via its RNase activity, and that this function (rather than dNTPase activity) is sufficient for HIV-1 restriction. While HIV-1 genomic RNA is a potent target for SAMHD1 during viral infection, the specificity of SAMHD1-mediated RNase activity during infection by other viruses is unclear. RESULTS: The results of the present study showed that SAMHD1 specifically degrades retroviral genomic RNA in monocyte-derived macrophage-like cells and in primary monocyte-derived macrophages. Consistent with this, SAMHD1 selectively restricted retroviral replication, but did not affect the replication of other common non-retro RNA genome viruses, suggesting that the RNase-mediated antiviral function of SAMHD1 is limited to retroviruses. In addition, neither inhibiting reverse transcription by treatment with several reverse transcriptase inhibitors nor infection with reverse transcriptase-defective HIV-1 altered RNA levels after viral challenge, indicating that the retrovirus-specific RNase function is not dependent on processes associated with retroviral reverse transcription. CONCLUSIONS: The results presented herein suggest that the RNase activity of SAMHD1 is sufficient to control the replication of retroviruses, but not that of non-retro RNA viruses.
Asunto(s)
Interacciones Huésped-Patógeno , Inmunidad Innata , Proteínas de Unión al GTP Monoméricas/metabolismo , ARN Viral/metabolismo , Retroviridae/inmunología , Ribonucleasas/metabolismo , Replicación Viral , Línea Celular , Humanos , Hidrólisis , Macrófagos/inmunología , Macrófagos/virología , Retroviridae/fisiología , Proteína 1 que Contiene Dominios SAM y HDRESUMEN
The human cytomegalovirus glycoprotein US2 induces dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol and targets them for proteasomal degradation. Signal peptide peptidase (SPP) has been shown to be integral for US2-induced dislocation of MHC class I heavy chains although its mechanism of action remains poorly understood. Here, we show that knockdown of protein disulphide isomerase (PDI) by RNA-mediated interference inhibited the degradation of MHC class I molecules catalysed by US2 but not by its functional homolog US11. Overexpression of the substrate-binding mutant of PDI, but not the catalytically inactive mutant, dominant-negatively inhibited US2-mediated dislocation of MHC class I molecules by preventing their release from US2. Furthermore, PDI associated with SPP independently of US2 and knockdown of PDI inhibited SPP-mediated degradation of CD3delta but not Derlin-1-dependent degradation of CFTR DeltaF508. Together, our data suggest that PDI is a component of the SPP-mediated ER-associated degradation machinery.
Asunto(s)
Ácido Aspártico Endopeptidasas/metabolismo , Citomegalovirus/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Células HeLa , Humanos , Proteínas de la Membrana/metabolismo , Mutación , Unión Proteica , Proteína Disulfuro Isomerasas/genética , Pliegue de Proteína , Interferencia de ARN , Proteínas de Unión al ARN/metabolismo , Especificidad por Sustrato , Proteínas Virales/metabolismoRESUMEN
In neutrophils, caspase-11 cleaves gasdermin D (GSDMD), causing pyroptosis to clear cytosol-invasive bacteria. In contrast, caspase-1 also cleaves GSDMD but seems to not cause pyroptosis. Here, we show that this pyroptosis-resistant caspase-1 activation is specifically programmed by the site of translocation of the detected microbial virulence factors. We find that pyrin and NLRC4 agonists do not trigger pyroptosis in neutrophils when they access the cytosol from endosomal compartment. In contrast, when the same ligands penetrate through the plasma membrane, they cause pyroptosis. Consistently, pyrin detects extracellular Yersinia pseudotuberculosis ΔyopM in neutrophils, driving caspase-1-GSDMD pyroptosis. This pyroptotic response drives PAD4-dependent H3 citrullination and results in extrusion of neutrophil extracellular traps (NETs). Our data indicate that caspase-1, GSDMD, or PAD4 deficiency renders mice more susceptible to Y. pseudotuberculosis ΔyopM infection. Therefore, neutrophils induce pyroptosis in response to caspase-1-activating inflammasomes triggered by extracellular bacterial pathogens, but after they phagocytose pathogens, they are programmed to forego pyroptosis.
Asunto(s)
Inflamasomas , Toxinas Biológicas , Ratones , Animales , Inflamasomas/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Neutrófilos/metabolismo , Pirina/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Caspasa 1/metabolismo , Caspasas/metabolismo , Bacterias/metabolismoRESUMEN
Shigella flexneri, a cytosol-invasive gram-negative pathogen, deploys an array of type III-secreted effector proteins to evade host cell defenses. Caspase-11 and its human ortholog caspase-4 detect cytosolic lipopolysaccharide (LPS) and trigger gasdermin D-mediated pyroptosis to eliminate intra-cytoplasmic bacterial threats. However, the role of caspase-11 in combating S. flexneri is unclear. The Shigella T3SS effector OspC3 reportedly suppresses cytosolic LPS sensing by inhibiting caspase-4 but not caspase-11 activity. Surprisingly, we found that S. flexneri also uses OspC3 to inhibit murine caspase-11 activity. Mechanistically, we found that OspC3 binds only to primed caspase-11. Importantly, we demonstrate that S. flexneri employs OspC3 to prevent caspase-11-mediated pyroptosis in neutrophils, enabling bacteria to disseminate and evade clearance following intraperitoneal challenge. In contrast, S. flexneri lacking OspC3 is attenuated in a caspase-11- and gasdermin D-dependent fashion. Overall, our study reveals that OspC3 suppresses cytosolic LPS detection in a broad array of mammals.
RESUMEN
Characterizing cytokine production in situ is important for properly understanding immunologic responses. Cytokine reporter mice are limited by the need to cross markers into various knockout backgrounds and by availability of reporters of interest. To overcome this, we utilize injection of brefeldin A into mice to enable flow cytometric analysis of in situ cytokine production during a bacterial infection. While we evaluate IFN-γ production during Burkholderia thailandensis infection, this protocol can be applied to other cytokines and other mouse models. For complete details on the use and execution of this protocol, please refer to Kovacs et al. (2020) and Liu and Whitton (2005).
Asunto(s)
Brefeldino A/química , Infecciones por Burkholderia/inmunología , Burkholderia/inmunología , Citometría de Flujo , Interferón gamma/inmunología , Animales , RatonesRESUMEN
The airway epithelium and underlying innate immune cells comprise the first line of host defense in the lung. They recognize pathogen-associated molecular patterns (PAMPs) using membrane-bound receptors, as well as cytosolic receptors such as inflammasomes. Inflammasomes activate inflammatory caspases, which in turn process and release the inflammatory cytokines IL-1ß and IL-18. Additionally, inflammasomes trigger a form of lytic cell death termed pyroptosis. One of the most important inflammasomes at the host-pathogen interface is the non-canonical caspase-11 inflammasome that responds to LPS in the cytosol. Caspase-11 is important in defense against Gram-negative pathogens, and can drive inflammatory diseases such as LPS-induced sepsis. However, pathogens can employ evasive strategies to minimize or evade host caspase-11 detection. In this review, we present a comprehensive overview of the function of the non-canonical caspase-11 inflammasome in sensing of cytosolic LPS, and its mechanism of action with particular emphasis in the role of caspase-11 in the lung. We also explore some of the strategies pathogens use to evade caspase-11.
Asunto(s)
Caspasas/metabolismo , Bacterias Gramnegativas/inmunología , Inmunidad Innata , Inflamasomas/metabolismo , Lipopolisacáridos/inmunología , Pulmón/enzimología , Neumonía Bacteriana/enzimología , Animales , Caspasa 1/inmunología , Caspasa 1/metabolismo , Caspasas/inmunología , Bacterias Gramnegativas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Inflamasomas/inmunología , Lipopolisacáridos/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Piroptosis , Transducción de SeñalRESUMEN
Either caspase-1 or caspase-11 can cleave gasdermin D to cause pyroptosis, eliminating intracellular replication niches. We previously showed that macrophages detect Burkholderia thailandensis via NLRC4, triggering the release of interleukin (IL)-18 and driving an essential interferon (IFN)-γ response that primes caspase-11. We now identify the IFN-γ-producing cells as a mixture of natural killer (NK) and T cells. Although both caspase-1 and caspase-11 can cleave gasdermin D in macrophages and neutrophils, we find that NLRC4-activated caspase-1 triggers pyroptosis in macrophages, but this pathway does not trigger pyroptosis in neutrophils. In contrast, caspase-11 triggers pyroptosis in both macrophages and neutrophils. This translates to an absolute requirement for caspase-11 in neutrophils during B. thailandensis infection in mice. We present an example of inflammasome sensors causing diverging outcomes in different cell types. Thus, cell fates are dictated not simply by the pathogen or inflammasome, but also by how the cell is wired to respond to detection events.
Asunto(s)
Caspasas Iniciadoras/metabolismo , Neutrófilos/metabolismo , Piroptosis/fisiología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Burkholderia/patogenicidad , Proteínas de Unión al Calcio/metabolismo , Caspasa 1/metabolismo , Caspasas/metabolismo , Citosol/metabolismo , Femenino , Inflamasomas/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/microbiología , Proteínas de Unión a Fosfato/metabolismo , Piroptosis/inmunologíaRESUMEN
Voiding cystourethrography (VCUG) demonstrates the anatomy of the urinary system and is used to detect the presence/absence of vesicoureteral reflux. It is the most important modality for urological fluoroscopic examination in children. For improved patient care, it is important to understand and perform VCUG appropriately. Therefore, an in-depth review of VCUG protocols and techniques has been presented herein. In addition, tips, tricks, and pitfalls associated with the technique have also been addressed.
RESUMEN
The autoimmune disorder Aicardi-Goutières syndrome (AGS) is characterized by a constitutive type I interferon response. SAMHD1 possesses both dNTPase and RNase activities and mutations in SAMHD1 cause AGS; however, how SAMHD1-deficiency causes the type I interferon response in patients with AGS remains unknown. Here, we show that endogenous RNA substrates accumulated in the absence of SAMHD1 act as a major immunogenic source for the type I interferon response. Reconstitution of SAMHD1-negative human cells with wild-type but not RNase-defective SAMHD1 abolishes spontaneous type I interferon induction. We further identify that the PI3K/AKT/IRF3 signaling pathway is essential for the type I interferon response in SAMHD1-deficient human monocytic cells. Treatment of PI3K or AKT inhibitors dramatically reduces the type I interferon signatures in SAMHD1-deficient cells. Moreover, SAMHD1/AKT1 double knockout relieves the type I interferon signatures to the levels observed for wild-type cells. Identification of AGS-related RNA sensing pathway provides critical insights into the molecular pathogenesis of the type I interferonopathies such as AGS and overlapping autoimmune disorders.
Asunto(s)
Estudios de Asociación Genética , Interferón Tipo I/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/deficiencia , Transducción de Señal , Animales , Línea Celular , Humanos , Factor 3 Regulador del Interferón/metabolismo , Ratones , Monocitos/metabolismo , Mutación , ARN/genética , ARN/metabolismo , Receptor de Interferón alfa y beta/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Proteína 1 que Contiene Dominios SAM y HD/metabolismoRESUMEN
The HIV-1 restriction factor SAM domain- and HD domain-containing protein 1 (SAMHD1) is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. However, phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction. Here, we show that SAMHD1 possesses RNase activity and that the RNase but not the dNTPase function is essential for HIV-1 restriction. By enzymatically characterizing Aicardi-Goutières syndrome (AGS)-associated SAMHD1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1 for defects in RNase or dNTPase activity, we identify SAMHD1 point mutants that cause loss of one or both functions. The RNase-positive and dNTPase-negative SAMHD1D137N mutant is able to restrict HIV-1 infection, whereas the RNase-negative and dNTPase-positive SAMHD1Q548A mutant is defective for HIV-1 restriction. SAMHD1 associates with HIV-1 RNA and degrades it during the early phases of cell infection. SAMHD1 silencing in macrophages and CD4(+) T cells from healthy donors increases HIV-1 RNA stability, rendering the cells permissive for HIV-1 infection. Furthermore, phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity in cells and impedes HIV-1 restriction. Our results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by directly degrading the HIV-1 RNA.
Asunto(s)
Infecciones por VIH/virología , VIH-1/fisiología , Proteínas de Unión al GTP Monoméricas/genética , Proteínas de Unión al GTP Monoméricas/metabolismo , ARN Viral/metabolismo , Replicación Viral , Enfermedades Autoinmunes del Sistema Nervioso/genética , Secuencia de Bases , Sitios de Unión/genética , Linfocitos T CD4-Positivos , Línea Celular Tumoral , Infecciones por VIH/genética , Células HeLa , Humanos , Macrófagos , Mutación , Malformaciones del Sistema Nervioso/genética , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Viral/genética , Ribonucleasas/metabolismo , Proteína 1 que Contiene Dominios SAM y HD , Análisis de Secuencia de ARNRESUMEN
Most antigenic peptides are generated by proteasomes in the cytosol and are transported by the transporter associated with antigen processing (TAP) into the endoplasmic reticulum, where they bind with nascent major histocompatibilitiy complex class I molecule (MHC-I). Although the overall process of peptide-MHC-I complex assembly is well studied, the mechanism by which free peptides are delivered from TAP to MHC-I is unknown. In this study, we investigated the possible role of protein disulfide isomerase (PDI) as a peptide carrier between TAP and MHC-I. Analysis of PDI-peptide complexes reconstituted in vitro showed that PDI exhibits some degree of specificity for peptides corresponding to antigenic ligands of various human leukocyte antigen (HLA) alleles. Mutations of either anchor residues of the peptide ligand or the peptide-binding site of PDI inhibited the PDI-peptide interaction. The PDI-peptide interaction increased under reducing conditions, whereas binding of the peptide to PDI decreased under oxidizing conditions. TAP-associated PDI was predominantly present in the reduced form, whereas the MHC-I-associated PDI was present in the oxidized form. Further, upon binding of optimal peptides, PDI was released from TAP and sequentially associated with HLA-A2.1. Our data revealed a redox-regulated chaperone function of PDI in delivering antigenic peptides from TAP to MHC-I.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antígenos de Histocompatibilidad Clase I/inmunología , Proteína Disulfuro Isomerasas/metabolismo , Transportadoras de Casetes de Unión a ATP/inmunología , Sitios de Unión/genética , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/metabolismo , Células HeLa , Humanos , Ligandos , Mutagénesis Sitio-Dirigida , Mutación , Oxidación-Reducción , Péptidos/inmunología , Péptidos/metabolismoRESUMEN
We proposed a spatially resolved optical emission spectrometer (SROES) for analyzing the uniformity of plasma density for semiconductor processes. To enhance the spatial resolution of the SROES, we constructed a SROES system using a series of lenses, apertures, and pinholes. We calculated the spatial resolution of the SROES for the variation of pinhole size, and our calculated results were in good agreement with the measured spatial variation of the constructed SROES. The performance of the SROES was also verified by detecting the correlation between the distribution of a fluorine radical in inductively coupled plasma etch process and the etch rate of a SiO(2) film on a silicon wafer.
RESUMEN
Proper folding and assembly of major histocompatibility complex (MHC) class I complexes are essential for optimal peptide loading and subsequent antigen presentation. MHC class I folding involves the coordinated formation of multiple disulfide bonds within MHC class I molecules. However, the regulation of disulfide bond formation during the early process of MHC class I folding is uncharacterized. Here, we show that protein disulfide isomerase (PDI) catalyzes the disulfide bond formation of MHC class I molecules and thereby facilitates the assembly of MHC class I heavy chain with beta(2)-microglobulin (beta(2)m). Depletion of PDI but not ERp57 by RNAi interfered with the disulfide bond formation in the MHC class I molecules. In the absence of PDI, the association of free class I heavy chain with calnexin increased, whereas the assembly of MHC class I heavy chain-beta(2)m heterodimers was delayed. These observations suggest that PDI-catalyzed disulfide bond formation of MHC class I molecules is an event downstream of the interaction of class I molecules with calnexin and upstream of their interaction with beta(2)m. Thus, our data establish a critical function for PDI in the early assembly of MHC class I molecules.
Asunto(s)
Genes MHC Clase I , Complejo Mayor de Histocompatibilidad , Proteína Disulfuro Isomerasas/metabolismo , Pliegue de Proteína , Animales , Línea Celular , Disulfuros/química , Células HeLa , Humanos , Complejo Mayor de Histocompatibilidad/genética , Modelos Biológicos , Proteína Disulfuro Isomerasas/genética , Microglobulina beta-2/química , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismoRESUMEN
Major histocompatibility complex (MHC) class I molecules present antigenic peptides to the cell surface for screening by CD8(+) T cells. A number of ER-resident chaperones assist the assembly of peptides onto MHC class I molecules, a process that can be divided into several steps. Early folding of the MHC class I heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m). The MHC class I heavy chain-beta(2)m heterodimer is incorporated into the peptide-loading complex, leading to peptide loading, release of the peptide-filled MHC class I molecules from the peptide-loading complex, and exit of the complete MHC class I complex from the ER. Because proper antigen presentation is vital for normal immune responses, the assembly of MHC class I molecules requires tight regulation. Emerging evidence indicates that thiol-based redox regulation plays critical roles in MHC class I-restricted antigen processing and presentation, establishing an unexpected link between redox biology and antigen processing. We review the influences of redox regulation on antigen processing and presentation. Because redox signaling pathways are a rich source of validated drug targets, newly discovered redox biology-mediated mechanisms of antigen processing may facilitate the development of more selective and therapeutic drugs or vaccines against immune diseases.