Peptidase inhibitor 16 identifies a human regulatory T-cell subset with reduced FOXP3 expression over the first year of recent onset type 1 diabetes
| Autor: | John Welch, Heddy Zola, Simon C. Barry, Doreen Krumbiegel, Daniel J. Campbell, Timothy Sadlon, Batjargal Gundsambuu, Cheryl Y. Brown, Grace Ang, Stephen Pederson, Jennefer J Couper, Randall Grosse, Danika L. Hill, Nicola Eastaff-Leung, Christoper M Hope, Arunesh Mohandas, Michael Papademetrios, Suzanne Bresatz, Thomas Duhen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Risk Adolescent Regulatory T cell Immunology Down-Regulation chemical and pharmacologic phenomena Biology medicine.disease_cause T-Lymphocytes Regulatory Autoimmunity Immune tolerance 03 medical and health sciences Young Adult 0302 clinical medicine Immune system Immunity T-Lymphocyte Subsets medicine Immune Tolerance Immunology and Allergy Humans Precision Medicine Child Glycoproteins Type 1 diabetes FOXP3 hemic and immune systems Forkhead Transcription Factors medicine.disease 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 Child Preschool CD4 Antigens Disease Progression Biomarker (medicine) Female Carrier Proteins Transcriptome Biomarkers 030215 immunology |
| Zdroj: | European journal of immunology. 49(8) |
| ISSN: | 1521-4141 |
| Popis: | CD4+ T-cell subsets play a major role in the host response to infection, and a healthy immune system requires a fine balance between reactivity and tolerance. This balance is in part maintained by regulatory T cells (Treg), which promote tolerance, and loss of immune tolerance contributes to autoimmunity. As the T cells which drive immunity are diverse, identifying and understanding how these subsets function requires specific biomarkers. From a human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as a CD4 subset biomarker and we now show detailed analysis of its distribution, phenotype and links to Treg function in type 1 diabetes. To determine the clinical relevance of Pi16 Treg, we analysed PI16+ Treg cells from type 1 diabetes patient samples. We observed that FOXP3 expression levels declined with disease progression, suggesting loss of functional fitness in these Treg cells in Type 1 diabetes, and in particular the rate of loss of FOXP3 expression was greatest in the PI16+ve Treg. We propose that PI16 has utility as a biomarker of functional human Treg subsets and may be useful for tracking loss of immune function in vivo. The ability to stratify at risk patients so that tailored interventions can be applied would open the door to personalised medicine for Type 1 diabetes. |
| Databáze: | OpenAIRE |
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