jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf The regulatory roles of optineurin in innate immunity: A Review

jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf The regulatory roles of optineurin in innate immunity: A Review | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 6 February 2025 V1 Latest version Share on jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf The regulatory roles of optineurin in innate immunity: A Review Authors : Jie Han , Ting Jiang , Chunfu Zheng 0000-0002-8797-1322 [email protected] , Mengzhou Xue , and Liting Zhang Authors Info & Affiliations https://doi.org/10.22541/au.173884101.11775156/v1 223 views 186 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Optineurin (OPTN) is a novel protein discovered by yeast two-hybrid screening. It has been linked to neurodegenerative illnesses such as glaucoma and amyotrophic lateral sclerosis (ALS) via its involvement in numerous signaling pathways. Research shows that this protein regulates the NF-κB, TBK1, and interferon signaling pathways, contributing to the body’s innate immune response. In this review, we consolidate recent research findings, define the role of OPTN in the innate immune response, outline its regulatory interactions with major innate immunity components, and address OPTN’s possible involvement in illness via innate immune processes. The regulatory roles of optineurin in innate immunity: A Review Jie Han 1, 2 , Ting Jiang 2 , Chunfu Zheng 4,* , Mengzhou Xue 3,* , Li-Ting Zhang 1, 2,* 1 Department of Central Laboratory, Changzhou Wujin People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213017, China. 2 Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Changzhou, 213017, China; 3 Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; 4 Department of Microbiology, Immunology & Infection Diseases, University of Calgary, Calgary, Alberta, Canada Correspondence to Liting Zhang ( [email protected] ) and Chunfu Zheng ( [email protected] ). Abstract Optineurin (OPTN) is a novel protein discovered by yeast two-hybrid screening. It has been linked to neurodegenerative illnesses such as glaucoma and amyotrophic lateral sclerosis (ALS) via its involvement in numerous signaling pathways. Research shows that this protein regulates the NF-κB, TBK1, and interferon signaling pathways, contributing to the body’s innate immune response. In this review, we consolidate recent research findings, define the role of OPTN in the innate immune response, outline its regulatory interactions with major innate immunity components, and address OPTN’s possible involvement in illness via innate immune processes. Keywords: Optineurin, innate immunity, regulation, NF-κB, IFN By employing various innate immune receptors, including cyclic GMP-AMP synthase (cGAS) and retinoic acid-inducible gene I (RIG-I), cells exhibit a sophisticated capacity to identify and protect their genetic material from external threats. The cGAS-STING pathway plays a crucial role in the immune response to cytoplasmic DNA. Upon detecting DNA, cGAS is activated and synthesizes cyclic GMP-AMP (cGAMP), a second messenger that binds to and activates the stimulator of interferon genes (STING) protein. STING then translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi apparatus, a process that relies on the COP-II complex. This activation leads to the recruitment of tank-binding kinase 1 (TBK1), which is essential for the phosphorylation of STING and the transcription factor IRF3, ultimately resulting in the production of type I interferons and other cytokines [1-5] . RIG-I is a pattern recognition receptor that detects dsRNA in the cytoplasm. RIG-I undergoes a conformational change that allows it to interact with the mitochondrial antiviral signaling protein (MAVS). This interaction is essential for stimulating TBK1, which in turn phosphorylates IRF3 [6] . The interaction between cGAS and RIG-I underscores the complex mechanisms that cells utilize to preserve genomic integrity and respond to external threats jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf [7] . TBK1 is a critical kinase that plays a significant role in the regulation of interferon production. In addition, this kinase is known to interact with IKKε and other components of the NF-κB signaling cascade, influencing immune responses and inflammation [8] . Understanding the multifaceted roles of TBK1 in these signaling pathways is crucial for developing therapeutic strategies aimed at modulating immune responses in various diseases, including viral infections and inflammatory disorders. OPTN is a multifunctional protein first identified in 1998 when researchers discovered it as a binding partner for the adenovirus E3 14.7 kDa protein through yeast two-hybrid screening; it was initially named FIP-2 (14.7K-interacting protein) [9] . Subsequent research into glaucoma revealed genetic mutations in OPTN in patients with primary open-angle glaucoma, leading to its renaming as ”optineurin,” indicative of its role in inducing optic neuropathy [10] . Further studies linked OPTN to other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [11, 12] , sparking increased academic interest in this protein. The OPTN is involved in various cellular processes, including the innate immune response, which serves as the body’s first line of defence against viral infections. This response is initiated by pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs), leading to the production of pro-inflammatory cytokines and type I interferons, which are crucial for antiviral defence [13, 14] . OPTN interacts with multiple signaling pathways and key factors in the innate immune process, and mutations in OPTN can alter these interactions, potentially disrupting normal signaling. In this review, we discuss the role of OPTN in the human innate immune process. We discuss its involvement in the NF-κB and interferon signaling pathways, its interactions with key innate immune factors such as TBK1, and its role in cellular functions such as autophagy. Finally, we explored autoimmune diseases associated with OPTN, highlighting its significance in both health and disease. Structure and characteristics of OPTN Optineurin (OPTN) is ubiquitously present in human tissues and cells as a multidomain protein capable of interacting with a variety of proteins to mediate diverse functions. The OPTN gene comprises a 5’ untranslated region (UTR) composed of three noncoding exons and a coding region consisting of 13 exons that encode a 66 kDa protein [15] . Selective splicing of its 5’-UTR results in four different isoforms with the same open reading frame [16] . Structurally, OPTN contains two coiled-coil (CC) domains, a basic leucine zipper motif (LZ), an LC3-interacting region (LIR), a ubiquitin-binding domain (UBAN), and a zinc finger domain at the C-terminus [17] (Fig. 1). This structure enables OPTN to interact with various proteins, thereby facilitating different cellular functions. Additionally, OPTN undergoes posttranslational modifications, including ubiquitination and phosphorylation, increasing the complexity of its functional roles [18] . To date, researchers have identified several binding partners of OPTN, including TANK-binding kinase 1 (TBK1) [19, 20] , tax1 binding protein 1 (TAX1BP1) [21] , LC3, and huntingtin protein (Htt) [22, 23] . These interactions, particularly with receptors such as TBK1, are closely linked to the human innate immune response. Moreover, the role of OPTN in autophagy has garnered increasing research interest. These findings underscore the significant role of OPTN in the innate immune processes of the human body. Fig. 1. Schematic representation of the human OPTN domains and the known sites that interact with other proteins. Optineurin contains two coiled-coil (CC) domains, a leucine zipper (LZ), an LC3-interacting region (LIR), the UBAN domain, and a zinc finger (ZF) domain at the C-terminus. To date, many studies have identified the interaction regions of optineurin with its binding partners. OPTN and NF-κB Signaling The NF-κB signaling pathway is crucial for activating the inflammatory response in humans and is a key component of the innate immune system. NF-κB essential modulator (NEMO) is a core regulatory component of the NF-κB kinase (IKK) complex, which is essential for NF-κB activation [24] . OPTN, which shares structural similarities with NEMO, including the ubiquitin-binding domain (UBD) of ABIN proteins, plays a significant role in this pathway [25] . In vitro experiments have shown that during tumor necrosis factor (TNF) activation of NF-κB signaling, OPTN competes with NEMO for binding to receptor-interacting protein kinase 1 (RIPK1), thereby inhibiting NF-κB signaling [24, 26] . The UBD of OPTN is crucial in this inhibitory process [27] . Additionally, interactions between OPTN and cylindromatosis (CYLD) have been demonstrated to block downstream NF-κB signaling [28] . OPTN similarly affects NF-κB signaling triggered by Toll-like receptors, where it binds to interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK-1) to prevent the formation of TRAF6 oligomers, thus inhibiting NF-κB signaling [29] . However, the role of OPTN in virus-activated NF-κB signaling differs significantly. In models of human T-lymphotropic virus type 1 (HTLV-1) infection, OPTN interacts with the viral oncoproteins Tax1 and TAX1BP1, regulating Tax1 ubiquitination and leading to sustained activation of NF-κB [21] . These experimental findings are based on in vitro studies. However, the role of OPTN has not been confirmed in vivo [30] . OPTN knockout mice still exhibit NF-κB-dependent inflammatory responses and can activate the NF-κB pathway through Toll-like receptors [30-32]22,23,24 . This discrepancy between the in vitro and in vivo results is not yet understood, possibly because of the overexpression or knockdown of OPTN in vitro or the indirect effects of OPTN interactions on NF-κB signaling (Fig. 2). jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf OPTN and Type I Interferon (IFN) Signaling Interferons (IFNs) are essential products of the human innate immune system in response to infections. When components of bacteria or viruses, such as double-stranded DNA (dsDNA), enter the body, they are sensed by pattern recognition receptors (PRRs), leading to the activation of downstream interferon regulatory factor 3 (IRF3) and subsequent IFN production to induce immune responses [33] . TBK1 and IKKε are crucial regulators of IRF3. Studies indicate that OPTN can influence IFN production by interacting with TBK1 [19] but that OPTN does not interact with IKKε [34] . In some in vitro experiments, OPTN has been shown to downregulate IFN. In HEK293 cells, increased levels of OPTN inhibit IFN-β induction triggered by viruses and dsRNA, whereas reducing OPTN expression has the opposite effect [34] . However, experiments in mice have shown different results. Bone marrow-derived macrophages from OPTN-deficient mice exhibit reduced levels of TBK1 and IRF3, impacting IFN production [25, 30] . Mutant mice lacking the ubiquitin-binding domain (UBD) [32] or the TBK1 24 interaction region of OPTN display similar outcomes. Furthermore, a study from 2017 suggested that OPTN binding to ubiquitin chains can promote the activation of the OPTN-TBK1 complex, leading to IFN production [35] . These findings highlight the complex role of OPTN in regulating IFN signaling pathways, with discrepancies between in vitro and in vivo observations. The interaction of OPTN with TBK1 and its involvement in IFN production underscores its importance in the innate immune response to infections (Fig. 2). OPTN and Autophagy Autophagy is the process by which cells engulf cellular material and fuse it with lysosomes for degradation [36] . In addition to its role in recycling cellular components, autophagy is a critical mechanism by which the human body combats bacterial invasion and is an essential component of the innate immune system. By degrading lysosomes, autophagy captures and removes intracellular bacteria or pathogens, protecting cells from infection [37] . This degradation pathway requires specific autophagy receptors for recognition, and OPTN can serve as such a receptor. OPTN connects the autophagosome membrane to the target to be degraded through its LC3-interacting region (LIR), facilitating recognition [38] . During Salmonella infection of HeLa cells, OPTN binds to ubiquitinated bacteria, recruiting TBK1 to phosphorylate itself and enhancing its binding affinity with LC3, aiding in the autophagic clearance of invading Salmonella [39] . The presence of TBK1 is crucial in this process, as TBK1 knockout leads to uncontrolled Salmonella replication [40] . In in vivo experiments with zebrafish and mice infected with Salmonella, knockout or knockdown of OPTN affects the ability to clear bacteria, increasing susceptibility to Salmonella infection [41] . These experiments confirmed the significant role of OPTN in protecting cells from bacterial infections through autophagy (Fig. 2). In addition to clearing invading pathogens, OPTN also participates in the autophagic clearance of damaged organelles, such as mitochondrial autophagy, within cells. Damaged mitochondria in the human body can be selectively cleared through autophagy, preserving normal mitochondrial function [42] . During mitochondrial autophagy, PTEN-induced kinase 1 (PINK1) is stabilized on the surface of damaged mitochondria and activates the E3 ubiquitin ligase Parkin [43] . Subsequently, Parkin recruits autophagy receptors through ubiquitin chain formation [44] . Moreover, damaged mitochondria recruit and activate TBK1 [45] , which further phosphorylates OPTN. Phosphorylated OPTN binds more tightly to different ubiquitin chains, acting as a guide for mitochondria to enter the autophagosome [38] (Fig. 2). However, OPTN is not the sole guiding factor in this process. Studies suggest that NDP52 is also an autophagy receptor for mitochondrial autophagy [46] . Cells lacking NDP52 exhibit significantly slower clearance of damaged mitochondria [47] . In diseases such as ALS, mutations in TBK1 and OPTN have been shown to inhibit autophagosome formation, affecting the efficiency of damaged mitochondria clearance. This discovery provides a possible pathological explanation for the involvement of OPTN in neurodegenerative diseases such as ALS, suggesting that inefficient mitochondrial turnover may contribute to neurodegenerative disorders [45] . The involvement of OPTN in selective autophagy can effectively suppress tumor development. In the preceding discussion, we explored the role of OPTN in mitochondrial autophagy. Impaired autophagy can lead to mitochondrial dysfunction and DNA damage, increasing the risk of DNA mutations and carcinogenesis [48] . This principle provides a possible explanation for the antitumor function of OPTN. Recent studies have shown that the tumor suppressor and E3 ubiquitin ligase HACE1 interact with OPTN, leading to the ubiquitination of OPTN and promoting its interaction with the autophagy receptor p62/SQSTM1 to form a complex. This interaction enhances autophagic flux and reduces DNA damage in the body [49] (Fig. 2). In vivo experiments in mice have also yielded similar conclusions, demonstrating that the interaction between OPTN and HACE1 effectively inhibits the growth of lung cancer cells [49] . Another study revealed that p62 and OPTN while acting as autophagy receptors, can also serve as autophagic substrates [49] . These findings shed light on the multifaceted role of OPTN in not only protecting cells from intracellular pathogens and maintaining mitochondrial health but also in suppressing tumor development through its involvement in selective autophagy. The interaction of OPTN with HACE1 and its impact on autophagic flux provides a promising avenue for exploring novel therapeutic strategies for cancer treatment. OPTN and Vesicle Transport Vesicle transport is a specialized mechanism for protein trafficking between cellular compartments, such as transporting proteins from the Golgi apparatus to lysosomes [50] . OPTN has also been found to play a role in vesicle transport. It interacts with the huntingtin protein (Htt) and the small GTPase Rab8 to regulate the transport of Golgi-derived vesicles to the plasma membrane 10 . Mutations in Htt that disrupt its binding with OPTN lead to defects in Golgi retrograde transport [51] . OPTN localized to the plasma membrane and Golgi vesicles can also interact with myosin VI, participating in membrane transport and endocytic processes [52] . Depletion of OPTN results in the loss of myosin VI in the Golgi complex, leading to Golgi fragmentation, highlighting the close relationship between OPTN and myosin VI [52] . Other studies have shown that OPTN, together with myosin VI, can regulate the opening of fusion pores, thereby controlling protein secretion [53] . During selective autophagy, myosin VI also cooperates with OPTN to transport inner membrane vesicles into the autophagosome, promoting autophagosome maturation [54] (Fig. 2). These findings demonstrate the multifunctional role of OPTN in vesicle transport, highlighting its involvement in Golgi transport, membrane trafficking, and secretion. The interaction between OPTN and myosin VI plays a crucial role in these processes and contributes to the maturation of autophagosomes during selective autophagy. Further exploration of the mechanisms underlying OPTN involvement in vesicle transport may provide valuable insights into cellular trafficking processes and potential therapeutic targets for related disorders. OPTN-related innate immune system diseases The relationship between OPTN and human innate immunity is complex, and its connection to many innate immune diseases remains unclear. Current studies on mutations in the OPTN gene have sparked widespread interest, suggesting a potential mechanism for OPTN involvement in innate immune diseases. Mutations in the OPTN gene have been identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and these mutations are linked to various pathways, such as the TBK1 and NF-κB pathways [12, 55, 56] . These findings suggest that these diseases may be caused by defects in OPTN’s innate immune pathways [11, 57, 58] . Certain mutations in TBK1 lead to a loss of binding ability with OPTN, affecting the formation of the OPTN-TBK1 complex and thereby inducing ALS [20] . Conversely, some mutations in OPTN, such as the E50K mutation, have been proven to be associated with glaucoma, where the binding capacity of OPTN with TBK1 is significantly increased [59] . In studies of ALS-related OPTN mutations, researchers have reported that these mutations often occur in the C-terminal region rather than the N-terminal TBK1 binding domain, indicating that the diseases caused by these mutations are not triggered by the TBK1 pathway [19] . The C-terminus of OPTN is related to its ubiquitin-binding function, suggesting that these mutations may promote disease development by affecting selective autophagy or the NF-κB pathway [19, 27] . OPTN can also inhibit necroptotic cell death by suppressing RIPK1 activity, thereby preventing neurodegenerative diseases such as ALS [60] . Similarly, in OPTN-deficient mice, symptoms of demyelination and axonal degeneration, which are characteristic of neuroinflammation and cell death, can be alleviated by inhibiting RIPK1 activity [60] . OPTN has also been found to bind with caspase 8 to prevent the activation of its downstream signaling, thereby inhibiting apoptosis [27] . Furthermore, OPTN has been linked to Crohn’s disease. Currently, a reduction in OPTN has been reported in approximately 10% of patients with Crohn’s disease [61, 62] . These patients’ macrophages exhibit a significant decrease in pro-inflammatory cytokine secretion, indicating that OPTN impacts inflammatory responses and bacterial clearance [61, 62] . Unlike bacteria-driven colitis, the sodium dextran sulfate-induced colitis model does not significantly change after OPTN knockout, suggesting that OPTN may have a specific role in preventing bacterial infections [41] . A recent study indicated that OPTN interacts with the ER stress sensor IRE1α, affecting the progression of Crohn’s disease [63] . Autophagy defects and ER stress in intestinal epithelial cells induce the aggregation of IRE1α, leading to intestinal inflammation. OPTN can induce the autophagic degradation of IRE1α, thereby inhibiting inflammation, suggesting a new potential long-term control mechanism for Crohn’s disease [64] . Fig. 2. The modulation of GAS-STING and RIG-I-MAVS pathways by OPTN. cGAS acts as a sensor for cytoplasmic dsDNA, leading to the production of cGAMP, which subsequently activates the STING pathway. Upon activation, STING translocates to the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) and Golgi apparatus, a process that is dependent on the COP-II complex. This translocation is essential for the activation of downstream signaling pathways, including the recruitment of TBK1, which phosphorylates STING and the transcription factor IRF3, ultimately leading to the production of type I interferons and other cytokines. Upon recognition of viral dsRNA, RIG-I initiates a signaling cascade that leads to the activation of MAVS, which subsequently activates TBK1. This activation is essential for the phosphorylation and activation of the transcription factor IRF3, which plays a pivotal role in the production of type I interferons and other antiviral responses. Moreover, IKKα and IKKβ are part of the IκB kinase (IKK) complex, which is primarily responsible for the phosphorylation and degradation of IκB proteins, thereby allowing the translocation of NF-κB dimers, such as P65, into the nucleus. (1) Endosomal and cytoplasmic viral DNA/RNAs are sensed by RLRs, triggering antiviral immune responses by mediating the recruitment of TBK1. TBK1 binds and phosphorylates OPTN, leading to IRF3 phosphorylation, dimerization, and nuclear translocation, thereby mediating the transcription of type I interferon response genes. (2) Upon activation of TNF receptor 1, OPTN is recruited to the receptor complex and competes with NEMO for ubiquitination of RIPK1. OPTN can also recruit the deubiquitinase CYLD, which cleaves ubiquitin chains from proteins such as NEMO and RIPK1, thereby blocking downstream NF-κB signaling. (3) OPTN acts as an autophagy receptor, binds to ubiquitin-coated cytoplasmic bacteria, and recruits TBK1 to phosphorylate OPTN, increasing its LC3 binding affinity and directing it to autophagosomal degradation. (4) Damaged mitochondria are removed through a selective mitophagy process mediated by the recruitment of the kinase PINK1 and the E3 ubiquitin ligase Parkin, which binds ubiquitin to outer membrane mitochondrial proteins, recruiting autophagy receptors such as OPTN for autophagosomal degradation of mitochondria. (5) OPTN is ubiquitinated by the tumor suppressor protein HACE1, promoting its interaction with p62 to form an autophagy receptor complex, accelerating autophagic flux. (6) OPTN coordinates endocytosis and membrane trafficking through interactions with Rab8, Htt, and myosin VI. Conclusion OPTN is involved in various signaling processes in the human body and affects multiple diseases. Since its discovery in patients with glaucoma, researchers have conducted extensive studies on this protein. Recent research has revealed the mechanisms by which OPTN participates in the innate immune processes of the human body. Innate immune responses are initiated through the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), leading to the production of pro-inflammatory cytokines and type I interferons through a series of signaling processes, with OPTN playing roles at multiple points in this pathway. In the innate immune system of the human body, OPTN participates in various ways: through the NF-κB signaling pathway, the TBK1-mediated IFN pathway, and autophagy pathways, and it is also involved in vesicle transport processes. These pathways can affect various functions in the body, including the regulation of autophagy, the modulation of inflammatory signals, and protection against cell death. These findings provide possible explanations for the links between OPTN and diseases such as glaucoma, ALS, and Crohn’s disease. Despite these advances, research on the relationship between OPTN and innate immunity still needs to be completed, and the mechanisms underlying OPTN mutations still need to be clarified. Currently, it is not possible to analyze the role of OPTN in the human body from a molecular mechanism perspective. To date, most findings have been observed in in vitro cell models without corresponding in vivo experimental data. Both OPTN-knockout and OPTN-mutant mice exhibit spontaneous disease, suggesting that OPTN is more likely to induce gain of function than loss of function, which complicates the study of certain diseases. Therefore, developing specific mutant OPTN knock-in models for particular diseases is crucial for further research into the relationship between OPTN and human innate immunity. Ethics Approval and Consent to participate Not applicable. Consent for publication Not applicable. Availability of data and Materials Not applicable. Competing interests The authors declare that they have no competing interests. jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Funding This work was supported by National Outstanding Youth Science Found Project of National Natural Science Foundation of China (82403003), China Postdoctoral Science Foundation (2024M751484), the Basic Research Project of Changzhou Medical Center of Nanjing Medical University (CMCB202310) and the Science and Technology Program of the Changzhou Health Commission (QN202340). Author’s Contributions LT Zhang, J Han, and CF Zheng contributed to the conception, design, analysis, and drafting of the manuscript. T Jiang and MZ Xue designed and illustrated figures. All authors approved the fnal version of the manuscript for submission. Acknowledgements Not applicable. References 1. Zhang C, Shang G, Gui X, Zhang X, Bai XC, Chen ZJ. Structural basis of STING binding with and phosphorylation by TBK1. Nature 2019 , 567(7748) : 394-398.2. 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Keywords cell activation immune deficiencies signal transduction Authors Affiliations Jie Han Changzhou Wujin People's Hospital View all articles by this author Ting Jiang Changzhou Wujin People's Hospital View all articles by this author Chunfu Zheng 0000-0002-8797-1322 [email protected] University of Calgary Department of Microbiology Immunology and Infectious Diseases View all articles by this author Mengzhou Xue Sichuan University West China Second University Hospital Department of Pediatrics View all articles by this author Liting Zhang Changzhou Wujin People's Hospital View all articles by this author Metrics & Citations Metrics Article Usage 223 views 186 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jie Han, Ting Jiang, Chunfu Zheng, et al. jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf The regulatory roles of optineurin in innate immunity: A Review. Authorea . 06 February 2025. 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