NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity

Sharfe, Nigel; Dalal, Ilan; Naghdi, Zahra; Lefaudeux, Diane; Vong, Linda; Dadi, Harjit; Navarro, Héctor I.; Tasher, Diana; Ovadia, Adi; Zangen, Tzili; Ater, Dorit; Ngan, Bo; Hoffmann, Alexander; Roifman, Chaim M.

doi:10.1016/j.jaut.2022.102946

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…FOXP1 was upregulated in death piglets and might aid viral replication. RELA and RELB are key TFs of the NFκB pathway, and their reduced expression leads to dysregulation of the NFκB pathway, resulting in severe autoimmune diseases and reduced immunity ( 57 ). RELA and RELB were upregulated in the death and resistance piglets and might help the host to resist PEDV by activating the NFκB pathway.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics yields valuable information regarding the response mechanisms of Chinese Min pigs infected with PEDV

Li,

Zhou,

Zhang

et al. 2023

Front. Vet. Sci.

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Porcine epidemic diarrhea virus (PEDV) causes porcine epidemic diarrhea (PED), a highly infectious disease, which has resulted in huge economic losses for the pig industry. To date, the pathogenic and immune response mechanism was not particularly clear. The purpose of this study was to investigate the pathogenic and immune responses of pigs infected with PEDV.In this study, 12 Min pigs were randomly selected without taking colostrum. At 3 days old, eight piglets were infected with 1 mL of PEDV solution (10 TCID50/ml), and the remaining four piglets were handled by 1 mL of 0.9% normal saline. Within the age of 7 days old, four piglets died and were considered as the death group. Correspondingly, four alive individuals were classified into the resistance group. Tissues of the duodenum, jejunum, ileum, colon, cecum, and rectum of piglets in the three groups were collected to measure the PEDV content. Additionally, the jejunum was used for the measurements and analyses of Hematoxylin-eosinstaining (HE), immunohistochemical sections, and transcriptomics. The phenotypes of Min piglets infected with PEDV showed that the viral copy numbers and jejunal damage had significant differences between the death and resistance groups. We also observed the transcriptome of the jejunum, and the differentially expressed (DE) analysis observed 6,585 DE protein-coding genes (PCGs), 3,188 DE long non-coding RNAs (lncRNAs), and 350 DE microRNAs (miRNAs), which were mainly involved in immune response and metabolic pathways. Furthermore, the specific expressed molecules for each group were identified, and 97 PCGs,108 lncRNAs, and 51 miRNAs were included in the ceRNA-regulated networks. By weighted gene co-expression network analysis (WGCNA) and transcription factor (TF) prediction, 27 significant modules and 32 significant motifs (E-value < 0.05) annotated with 519 TFs were detected. Of these TFs, 53 were DE PCGs. In summary, the promising key PCGs, lncRNAs, and miRNAs related to the pathogenic and immunological response of pigs infected with PEDV were detected and provided new insights into the pathogenesis of PEDV.

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Section: Discussionmentioning

confidence: 99%

Transcriptomics yields valuable information regarding the response mechanisms of Chinese Min pigs infected with PEDV

Li,

Zhou,

Zhang

et al. 2023

Front. Vet. Sci.

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“…We then investigated the presence of auto-Abs against type I IFNs in patients with other inborn errors of the alternative NF-κB pathway (AR complete NIK deficiency (n=2 from 2 kindreds 74 and unpublished); AR partial (n=4 from 2 kindreds) or complete (n=4 from 2 kindreds) RelB deficiency [74][75][76]101,102 and unpublished results), or the related TNFR (AR complete BAFFR deficiency (n=1 101 ); or XR partial CD40L deficiency (n=3 from 3 kindreds (unpublished)). No plasma from AR IKK-α deficient patients was available.…”

Section: Neutralizing Auto-abs Against Type I Ifns In Patients With N...mentioning

confidence: 99%

Impaired thymic AIRE expression underlies autoantibodies against type I IFNs in humans with inborn errors of the alternative NF-kB pathway

Voyer

Gervais

Rosain

et al. 2023

Preprint

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“…Of note, AD NFKB2 deficiency causes CID that has not been associated with abnormalities in memory T cells [40]. RELB deficiency results in a 'classical' CID with decreased proportions of na€ ıve CD4 þ T cells, rare thymus emigrants and accumulation of central memory T cells, thus suggesting that RELB is not required for T-cell memory [41,42].…”

Section: Defects In the Alternative Pathwaymentioning

confidence: 99%

Inborn errors of immunity underlying defective T-cell memory

Boutboul,

Picard,

Latour

2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review T-cell memory is a complex process not well understood involving specific steps, pathways and different T-cell subpopulations. Inborn errors of immunity (IEIs) represent unique models to decipher some of these requirements in humans. More than 500 different IEIs have been reported to date, and recently a subgroup of monogenic disorders characterized by memory T-cell defects has emerged, providing novel insights into the pathways of T-cell memory generation and maintenance, although this new knowledge is mostly restricted to peripheral blood T-cell memory populations. Recent findings This review draws up an inventory of the main and recent IEIs associated with T-cell memory defects and their mice models, with a particular focus on the nuclear factor kappa B (NF-κB) signalling pathway, including the scaffold protein capping protein regulator and myosin 1 linker 2 (CARMIL2) and the T-cell co-stimulatory molecules CD28 and OX-40. Besides NF-κB, IKZF1 (IKAROS), a key transcription factor of haematopoiesis and STAT3-dependent interleukin-6 signals involving the transcription factor ZNF341 also appear to be important for the generation of T cell memory. Somatic reversion mosaicism in memory T cells is documented for several gene defects supporting the critical role of these factors in the development of memory T cells with a potential clinical benefit. Summary Systematic examination of T-cell memory subsets could be helpful in the diagnosis of IEIs.

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NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity

Cited by 8 publications

References 27 publications

Transcriptomics yields valuable information regarding the response mechanisms of Chinese Min pigs infected with PEDV

Transcriptomics yields valuable information regarding the response mechanisms of Chinese Min pigs infected with PEDV

Impaired thymic AIRE expression underlies autoantibodies against type I IFNs in humans with inborn errors of the alternative NF-kB pathway

Inborn errors of immunity underlying defective T-cell memory

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