Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice
NLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of Nlrp12 in autoimmune-prone B6.Faslpr/lpr mice ameliorated autoimmunity in males but not females....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120958/full |
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| author | Leila Abdelhamid Leila Abdelhamid Jiangdi Mao Xavier Cabana-Puig Jing Zhu Brianna K. Swartwout Michael R. Edwards James C. Testerman Jacquelyn S. Michaelis Irving Coy Allen S. Ansar Ahmed Xin M. Luo |
| author_facet | Leila Abdelhamid Leila Abdelhamid Jiangdi Mao Xavier Cabana-Puig Jing Zhu Brianna K. Swartwout Michael R. Edwards James C. Testerman Jacquelyn S. Michaelis Irving Coy Allen S. Ansar Ahmed Xin M. Luo |
| author_sort | Leila Abdelhamid |
| collection | DOAJ |
| description | NLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of Nlrp12 in autoimmune-prone B6.Faslpr/lpr mice ameliorated autoimmunity in males but not females. Nlrp12 deficiency dampened B cell terminal differentiation, germinal center reaction, and survival of autoreactive B cells leading to decreased production of autoantibodies and reduced renal deposition of IgG and complement C3. In parallel, Nlrp12 deficiency reduced the expansion of potentially pathogenic T cells, including double-negative T cells and T follicular helper cells. Furthermore, reduced pro-inflammatory innate immunity was observed, where the gene deletion decreased in-vivo expansion of splenic macrophages and mitigated ex-vivo responses of bone marrow-derived macrophages and dendritic cells to LPS stimulation. Interestingly, Nlrp12 deficiency altered the diversity and composition of fecal microbiota in both male and female B6/lpr mice. Notably, however, Nlrp12 deficiency significantly modulated small intestinal microbiota only in male mice, suggesting that the sex differences in disease phenotype might be gut microbiota-dependent. Together, these results suggest a potential pathogenic role of NLRP12 in promoting systemic autoimmunity in males. Future studies will investigate sex-based mechanisms through which NLRP12 differentially modulates autoimmune outcomes. |
| first_indexed | 2024-04-10T04:34:17Z |
| format | Article |
| id | doaj.art-dd382a1d80b7478a870adf2346572e6d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T04:34:17Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dd382a1d80b7478a870adf2346572e6d2023-03-10T05:10:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11209581120958Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male miceLeila Abdelhamid0Leila Abdelhamid1Jiangdi Mao2Xavier Cabana-Puig3Jing Zhu4Brianna K. Swartwout5Michael R. Edwards6James C. Testerman7Jacquelyn S. Michaelis8Irving Coy Allen9S. Ansar Ahmed10Xin M. Luo11Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Microbiology, College of Veterinary Medicine, Alexandria University, Alexandria, EgyptDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesNLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of Nlrp12 in autoimmune-prone B6.Faslpr/lpr mice ameliorated autoimmunity in males but not females. Nlrp12 deficiency dampened B cell terminal differentiation, germinal center reaction, and survival of autoreactive B cells leading to decreased production of autoantibodies and reduced renal deposition of IgG and complement C3. In parallel, Nlrp12 deficiency reduced the expansion of potentially pathogenic T cells, including double-negative T cells and T follicular helper cells. Furthermore, reduced pro-inflammatory innate immunity was observed, where the gene deletion decreased in-vivo expansion of splenic macrophages and mitigated ex-vivo responses of bone marrow-derived macrophages and dendritic cells to LPS stimulation. Interestingly, Nlrp12 deficiency altered the diversity and composition of fecal microbiota in both male and female B6/lpr mice. Notably, however, Nlrp12 deficiency significantly modulated small intestinal microbiota only in male mice, suggesting that the sex differences in disease phenotype might be gut microbiota-dependent. Together, these results suggest a potential pathogenic role of NLRP12 in promoting systemic autoimmunity in males. Future studies will investigate sex-based mechanisms through which NLRP12 differentially modulates autoimmune outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120958/fullNLRP12gut microbiotaautoimmunitysex dependencepathogenic T cells |
| spellingShingle | Leila Abdelhamid Leila Abdelhamid Jiangdi Mao Xavier Cabana-Puig Jing Zhu Brianna K. Swartwout Michael R. Edwards James C. Testerman Jacquelyn S. Michaelis Irving Coy Allen S. Ansar Ahmed Xin M. Luo Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice Frontiers in Immunology NLRP12 gut microbiota autoimmunity sex dependence pathogenic T cells |
| title | Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice |
| title_full | Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice |
| title_fullStr | Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice |
| title_full_unstemmed | Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice |
| title_short | Nlrp12 deficiency alters gut microbiota and ameliorates Faslpr-mediated systemic autoimmunity in male mice |
| title_sort | nlrp12 deficiency alters gut microbiota and ameliorates faslpr mediated systemic autoimmunity in male mice |
| topic | NLRP12 gut microbiota autoimmunity sex dependence pathogenic T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120958/full |
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