Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease
We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. Th...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Candelaria Ponce-de-León Pedro Lorite Miguel Ángel López-Casado Pablo Mora Teresa Palomeque María Isabel Torres |
| author_facet | Candelaria Ponce-de-León Pedro Lorite Miguel Ángel López-Casado Pablo Mora Teresa Palomeque María Isabel Torres |
| author_sort | Candelaria Ponce-de-León |
| collection | DOAJ |
| description | We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the <i>PI3</i> gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200–CD200R axis and <i>PI3</i> in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of <i>PI3</i> in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the <i>PI3</i> genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the <i>PI3</i> gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease. |
| first_indexed | 2024-03-08T09:53:43Z |
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| language | English |
| last_indexed | 2024-03-08T09:53:43Z |
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| spelling | doaj.art-4ad81b0c6f07419085feb5743a9ecea32024-01-29T13:55:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125285210.3390/ijms25020852Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac DiseaseCandelaria Ponce-de-León0Pedro Lorite1Miguel Ángel López-Casado2Pablo Mora3Teresa Palomeque4María Isabel Torres5Department of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, SpainDepartment of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, SpainDepartment of Pediatric Gastroenterology, Virgen de las Nieves Hospital, 18014 Granada, SpainDepartment of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, SpainDepartment of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, SpainDepartment of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, SpainWe comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the <i>PI3</i> gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200–CD200R axis and <i>PI3</i> in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of <i>PI3</i> in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the <i>PI3</i> genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the <i>PI3</i> gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.https://www.mdpi.com/1422-0067/25/2/852CD200/CD200RElafinceliac diseasegluten peptidesimmune checkpoint |
| spellingShingle | Candelaria Ponce-de-León Pedro Lorite Miguel Ángel López-Casado Pablo Mora Teresa Palomeque María Isabel Torres Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease International Journal of Molecular Sciences CD200/CD200R Elafin celiac disease gluten peptides immune checkpoint |
| title | Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease |
| title_full | Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease |
| title_fullStr | Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease |
| title_full_unstemmed | Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease |
| title_short | Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease |
| title_sort | expression of elafin and cd200 as immune checkpoint molecules involved in celiac disease |
| topic | CD200/CD200R Elafin celiac disease gluten peptides immune checkpoint |
| url | https://www.mdpi.com/1422-0067/25/2/852 |
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