Impaired SNX9 Expression in Immune Cells during Chronic Inflammation: Prognostic and Diagnostic Implications
| Autor: | Michal Baniyash, Eliran Ish-Shalom, Julia Kanterman, Moshe Sade-Feldman, Olga Mizrahi, Yaron Meirow, Lynn Wang, Yair Klieger |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine CD3 Complex medicine.medical_treatment Immunology Arthritis Inflammation Biology Arthritis Rheumatoid Immunocompromised Host Mice 03 medical and health sciences Th2 Cells Immune system Downregulation and upregulation Biomarkers Tumor medicine Animals Humans Immunology and Allergy Myeloid Cells Melanoma Sorting Nexins Cells Cultured Cell Proliferation Autoimmune disease Mice Inbred BALB C Cancer Immunosuppression Th1 Cells medicine.disease Mice Inbred C57BL Disease Models Animal Chronic infection 030104 developmental biology Mice Inbred DBA Cancer research Leishmaniasis Visceral Female medicine.symptom Colorectal Neoplasms Leishmania donovani |
| Zdroj: | The Journal of Immunology. 196:156-167 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402877 |
| Popis: | Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition. We found that myeloid-derived suppressor cells, which are elevated in the course of chronic inflammation, are responsible for the observed SNX9 reduced expression. Moreover, SNX9 downregulation is reversible, as its expression levels return to normal and immune functions are restored when the inflammatory response and/or myeloid-derived suppressor cells are neutralized. SNX9 downregulation was detected in numerous mouse models for pathologies characterized by chronic inflammation such as chronic infection (Leishmania donovani), cancer (melanoma and colorectal carcinoma), and an autoimmune disease (rheumatoid arthritis). Interestingly, reduced levels of SNX9 were also observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host’s immune status and inflammatory stage. Our new discovery of SNX9 as being regulated by chronic inflammation and its association with immunosuppression, in addition to the CD247 regulation under such conditions, show the global impact of chronic inflammation and the generated immune environment on different cellular pathways in a diverse spectrum of diseases. |
| Databáze: | OpenAIRE |
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