CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus
This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with the autoimmune response in Cd38-/- mice compared to wild-type (WT) mice within the bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate...
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Frontiers Media S.A.
2025-02-01
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| author | Mercedes Zubiaur Laura C. Terrón-Camero Fernando Gordillo-González Eduardo Andrés-León Alicia Barroso-del Jesús Luz María Canet-Antequera María M. Pérez Sánchez-Cañete África Martínez-Blanco Marilú Domínguez-Pantoja María Botia-Sánchez Sonia Pérez-Cabrera Nerea Bello-Iglesias Antonio Alcina Ana-Clara Abadía-Molina Fuencisla Matesanz Esther Zumaquero Ramón Merino Jaime Sancho |
| author_facet | Mercedes Zubiaur Laura C. Terrón-Camero Fernando Gordillo-González Eduardo Andrés-León Alicia Barroso-del Jesús Luz María Canet-Antequera María M. Pérez Sánchez-Cañete África Martínez-Blanco Marilú Domínguez-Pantoja María Botia-Sánchez Sonia Pérez-Cabrera Nerea Bello-Iglesias Antonio Alcina Ana-Clara Abadía-Molina Fuencisla Matesanz Esther Zumaquero Ramón Merino Jaime Sancho |
| author_sort | Mercedes Zubiaur |
| collection | DOAJ |
| description | This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with the autoimmune response in Cd38-/- mice compared to wild-type (WT) mice within the bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) and spleen cells (SPC) at two and four weeks following adoptive cell transfer. We also analyzed cells from healthy, untreated mice. These analyses revealed a sustained upregulation of a transcriptional profile of purinergic receptors and ectonucleotidases in cGVHD WT PECs, which displayed a coordinated expression with several type I interferon-stimulated genes (ISGs) and with key molecules involved in the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, two hallmarks in the lupus pathology. A second purinergic receptor transcriptomic profile, which included P2rx7 and P2rx4, showed a coordinated gene expression of the components of the NLRP3 inflammasome with its potential activators. These processes were transcriptionally less active in cGVHD Cd38-/- PECs than in WT PECs. We have also shown evidence of a distinct enrichment in pathways signatures that define processes such as Ca2+ ion homeostasis, cell division, phagosome, autophagy, senescence, cytokine/cytokine receptor interactions, Th17 and Th1/Th2 cell differentiation in Cd38-/- versus WT samples, which reflected the milder inflammatory and autoimmune response elicited in Cd38-/- mice relative to WT counterparts in response to the allogeneic challenge. Last, we have shown an intense metabolic reprogramming toward oxidative phosphorylation in PECs and SPC from cGVHD WT mice, which may reflect an increased cellular demand for oxygen consumption, in contrast to PECs and SPC from cGVHD Cd38-/- mice, which showed a short-lived metabolic effect at the transcriptomic level. Overall, these findings support the pro-inflammatory and immunomodulatory role of CD38 during the development of the cGVHD-lupus disease. |
| format | Article |
| id | doaj-art-8c87c83a29754473b940a177f28723d0 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-8c87c83a29754473b940a177f28723d02025-02-10T06:48:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14419811441981CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupusMercedes Zubiaur0Laura C. Terrón-Camero1Fernando Gordillo-González2Eduardo Andrés-León3Alicia Barroso-del Jesús4Luz María Canet-Antequera5María M. Pérez Sánchez-Cañete6África Martínez-Blanco7Marilú Domínguez-Pantoja8María Botia-Sánchez9Sonia Pérez-Cabrera10Nerea Bello-Iglesias11Antonio Alcina12Ana-Clara Abadía-Molina13Fuencisla Matesanz14Esther Zumaquero15Ramón Merino16Jaime Sancho17Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainBioinformatics Unit, IPBLN, CSIC, Granada, SpainBioinformatics Unit, IPBLN, CSIC, Granada, SpainBioinformatics Unit, IPBLN, CSIC, Granada, SpainGenomics, IPBLN, CSIC, Granada, SpainGenomics, IPBLN, CSIC, Granada, SpainFlow Cytometry, IPBLN, CSIC, Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Biochemistry, Molecular Biology and Immunology III, School of Medicine, University of Granada (UGR), Granada, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainDepartment of Microbiology, University of Alabama at Birmingham (UAB), Birmingham, AL, United StatesDepartment of Cell and Molecular Signaling, Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), University of Cantabria (UC) and CSIC, Santander, SpainDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Granada, SpainThis study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with the autoimmune response in Cd38-/- mice compared to wild-type (WT) mice within the bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) and spleen cells (SPC) at two and four weeks following adoptive cell transfer. We also analyzed cells from healthy, untreated mice. These analyses revealed a sustained upregulation of a transcriptional profile of purinergic receptors and ectonucleotidases in cGVHD WT PECs, which displayed a coordinated expression with several type I interferon-stimulated genes (ISGs) and with key molecules involved in the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, two hallmarks in the lupus pathology. A second purinergic receptor transcriptomic profile, which included P2rx7 and P2rx4, showed a coordinated gene expression of the components of the NLRP3 inflammasome with its potential activators. These processes were transcriptionally less active in cGVHD Cd38-/- PECs than in WT PECs. We have also shown evidence of a distinct enrichment in pathways signatures that define processes such as Ca2+ ion homeostasis, cell division, phagosome, autophagy, senescence, cytokine/cytokine receptor interactions, Th17 and Th1/Th2 cell differentiation in Cd38-/- versus WT samples, which reflected the milder inflammatory and autoimmune response elicited in Cd38-/- mice relative to WT counterparts in response to the allogeneic challenge. Last, we have shown an intense metabolic reprogramming toward oxidative phosphorylation in PECs and SPC from cGVHD WT mice, which may reflect an increased cellular demand for oxygen consumption, in contrast to PECs and SPC from cGVHD Cd38-/- mice, which showed a short-lived metabolic effect at the transcriptomic level. Overall, these findings support the pro-inflammatory and immunomodulatory role of CD38 during the development of the cGVHD-lupus disease.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1441981/fullCD38purinergic-signalingcGAS-STINGNLRP3-inflammasometype I IFN signaturecGVHD lupus model |
| spellingShingle | Mercedes Zubiaur Laura C. Terrón-Camero Fernando Gordillo-González Eduardo Andrés-León Alicia Barroso-del Jesús Luz María Canet-Antequera María M. Pérez Sánchez-Cañete África Martínez-Blanco Marilú Domínguez-Pantoja María Botia-Sánchez Sonia Pérez-Cabrera Nerea Bello-Iglesias Antonio Alcina Ana-Clara Abadía-Molina Fuencisla Matesanz Esther Zumaquero Ramón Merino Jaime Sancho CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus Frontiers in Immunology CD38 purinergic-signaling cGAS-STING NLRP3-inflammasome type I IFN signature cGVHD lupus model |
| title | CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus |
| title_full | CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus |
| title_fullStr | CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus |
| title_full_unstemmed | CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus |
| title_short | CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus |
| title_sort | cd38 deficiency leads to a defective short lived transcriptomic response to chronic graft versus host disease induction involving purinergic signaling related genes and distinct transcriptomic signatures associated with lupus |
| topic | CD38 purinergic-signaling cGAS-STING NLRP3-inflammasome type I IFN signature cGVHD lupus model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1441981/full |
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