Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response
Decompression sickness (DCS) with neurological disorders includes an inappropriate inflammatory response which degenerates slowly, even after the disappearance of the bubbles. There is high inter-individual variability in terms of the occurrence of DCS that could have been mastered by the selection...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1253856/full |
| _version_ | 1828717292136955904 |
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| author | Nicolas Vallée Emmanuel Dugrenot Anne-Virginie Desruelle Simone Richard Stéphane Coupé Céline Ramdani Régis Guieu Jean-Jacques Risso Sandrine Gaillard François Guerrero |
| author_facet | Nicolas Vallée Emmanuel Dugrenot Anne-Virginie Desruelle Simone Richard Stéphane Coupé Céline Ramdani Régis Guieu Jean-Jacques Risso Sandrine Gaillard François Guerrero |
| author_sort | Nicolas Vallée |
| collection | DOAJ |
| description | Decompression sickness (DCS) with neurological disorders includes an inappropriate inflammatory response which degenerates slowly, even after the disappearance of the bubbles. There is high inter-individual variability in terms of the occurrence of DCS that could have been mastered by the selection and then the breeding of DCS-resistant rats. We hypothesized the selection of single-nucleotide polymorphisms (SNPs) linked to autoimmunity operated upon a generation of a DCS-resistant strain of rats. We used the candidate gene approach and targeted SNPs linked to the signaling cascade that directly regulates inflammation of innate immunity transiting by the Toll-like receptors. Twenty candidate SNPs were investigated in 36 standard rats and 33 DCS-resistant rats. For the first time, we identify a diplotype (i.e., with matched haplotypes)—when coinherited—that strengthens protection against DCS, which is not strictly homozygous and suggests that a certain tolerance may be considered. We deduced an ideal haplotype of six variants from it (MyD88_50-T, _49-A, _97-C coupled to NFKB_85-T, _69-T, _45-T) linked to the resistant phenotype. Four among the six identified variants are located in pre- and/or post-transcriptional areas regulating MyD88 or NFKB1 expression. Because of missense mutations, the other two variants induce a structural change in the NFKB1 protein complex including one damage alteration according to the Missense3D algorithm. In addition to the MyD88/NFKB1 haplotype providing rats with a strong resistance to DCS, this also highlights the importance that the immune response, here linked to the genetic heritage, can have in the development of DCS and offer a new perspective for therapeutic strategies. |
| first_indexed | 2024-03-12T14:26:01Z |
| format | Article |
| id | doaj.art-1f0c121d30e84ace95f2e400e5c055ac |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-12T14:26:01Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-1f0c121d30e84ace95f2e400e5c055ac2023-08-18T07:28:37ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-08-011410.3389/fphys.2023.12538561253856Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune responseNicolas Vallée0Emmanuel Dugrenot1Anne-Virginie Desruelle2Simone Richard3Stéphane Coupé4Céline Ramdani5Régis Guieu6Jean-Jacques Risso7Sandrine Gaillard8François Guerrero9Institut de Recherche Biomédicale des Armées, Equipe de Recherche Subaquatique Opérationnelle, Toulon, FranceUniversité de Brest Occidentale, ORPHY, IBSAM, Brest, FranceInstitut de Recherche Biomédicale des Armées, Equipe de Recherche Subaquatique Opérationnelle, Toulon, FranceUniversité de Toulon, La Garde, FranceUniversité de Toulon, La Garde, FranceInstitut de Recherche Biomédicale des Armées, Equipe de Recherche Subaquatique Opérationnelle, Toulon, FranceUniversité d’Aix-Marseille, Marseille, FranceInstitut de Recherche Biomédicale des Armées, Equipe de Recherche Subaquatique Opérationnelle, Toulon, FranceUniversité de Toulon, La Garde, FranceUniversité de Brest Occidentale, ORPHY, IBSAM, Brest, FranceDecompression sickness (DCS) with neurological disorders includes an inappropriate inflammatory response which degenerates slowly, even after the disappearance of the bubbles. There is high inter-individual variability in terms of the occurrence of DCS that could have been mastered by the selection and then the breeding of DCS-resistant rats. We hypothesized the selection of single-nucleotide polymorphisms (SNPs) linked to autoimmunity operated upon a generation of a DCS-resistant strain of rats. We used the candidate gene approach and targeted SNPs linked to the signaling cascade that directly regulates inflammation of innate immunity transiting by the Toll-like receptors. Twenty candidate SNPs were investigated in 36 standard rats and 33 DCS-resistant rats. For the first time, we identify a diplotype (i.e., with matched haplotypes)—when coinherited—that strengthens protection against DCS, which is not strictly homozygous and suggests that a certain tolerance may be considered. We deduced an ideal haplotype of six variants from it (MyD88_50-T, _49-A, _97-C coupled to NFKB_85-T, _69-T, _45-T) linked to the resistant phenotype. Four among the six identified variants are located in pre- and/or post-transcriptional areas regulating MyD88 or NFKB1 expression. Because of missense mutations, the other two variants induce a structural change in the NFKB1 protein complex including one damage alteration according to the Missense3D algorithm. In addition to the MyD88/NFKB1 haplotype providing rats with a strong resistance to DCS, this also highlights the importance that the immune response, here linked to the genetic heritage, can have in the development of DCS and offer a new perspective for therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fphys.2023.1253856/full3′UTR5′UTRautoimmunedecompression sicknessdivehyperoxia (oxygen) |
| spellingShingle | Nicolas Vallée Emmanuel Dugrenot Anne-Virginie Desruelle Simone Richard Stéphane Coupé Céline Ramdani Régis Guieu Jean-Jacques Risso Sandrine Gaillard François Guerrero Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response Frontiers in Physiology 3′UTR 5′UTR autoimmune decompression sickness dive hyperoxia (oxygen) |
| title | Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response |
| title_full | Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response |
| title_fullStr | Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response |
| title_full_unstemmed | Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response |
| title_short | Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response |
| title_sort | highlighting of the interactions of myd88 and nfkb1 snps in rats resistant to decompression sickness toward an autoimmune response |
| topic | 3′UTR 5′UTR autoimmune decompression sickness dive hyperoxia (oxygen) |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1253856/full |
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