Mesenchymal stem cells and a vitamin D receptor agonist additively suppress T helper 17 cells and the related inflammatory response in the kidney
| Autor: | Bairbre McNicholas, Howard O. Fearnhead, Michelle M. Duffy, David A. Monaghan, Matthew D. Griffin, Senthilkumar Alagesan, Jana Pindjakova, Shirley A. Hanley, Jill McMahon |
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| Rok vydání: | 2014 |
| Předmět: |
Agonist
Time Factors Physiology medicine.drug_class Inflammatory response Cellular differentiation Anti-Inflammatory Agents Inflammation Kidney Mesenchymal Stem Cell Transplantation Calcitriol receptor Vitamin D and neurology Medicine Animals Cells Cultured Nephritis business.industry Macrophages Mesenchymal stem cell Interleukin-17 Fibrosis Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Neutrophil Infiltration Immunology Ergocalciferols Cancer research Receptors Calcitriol Th17 Cells Female medicine.symptom business Biomarkers Immunosuppressive Agents Ureteral Obstruction |
| Zdroj: | American journal of physiology. Renal physiology. 307(12) |
| ISSN: | 1522-1466 |
| Popis: | Mesenchymal stem cells (MSCs) suppress T helper (Th)17 cell differentiation and are being clinically pursued for conditions associated with aberrant Th17 responses. Whether such immunomodulatory effects are enhanced by coadministration of MSCs with other agents is not well known. In the present study, individual and combined effects of MSCs and the vitamin D receptor (VDR) agonist paricalcitol on Th17 induction were investigated in vitro and in a mouse model of sterile kidney inflammation (unilateral ureteral obstruction). In vitro, MSCs and paricalcitol additively suppressed Th17 differentiation, although only MSCs suppressed expression of Th17-associated transcriptions factors. Combined administration of MSCs and paricalcitol resulted in an early ( day 3) reduction of intrarenal CD4+and CD8+T cells, CD11b+/lymphocyte antigen 6G+neutrophils, and inflammatory (lymphocyte antigen 6Chi) monocytes as well as reduced transcript for IL-17 compared with untreated animals. Later ( day 8), obstructed kidneys of MSC/paricalcitol double-treated mice, but not mice treated with either intervention alone, had reduced tubular injury and interstitial fibrosis as well as lower numbers of neutrophils and inflammatory monocytes and an increase in the ratio between M2 (CD206+) and M1 (CD206−) macrophages compared with control mice. Adjunctive therapy with VDR agonists may enhance the immunosuppressive properties of MSCs in the setting of pathogenic Th17-type immune responses and related inflammatory responses. |
| Databáze: | OpenAIRE |
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