Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin
| Autor: | Michael S. Ball, Jongmin Lee, Ainah U. Tan, Sapna M. Amin, Patricia A. Pioli, Yolanda Nesbeth, Tammara A. Wood, Diana M. Toledo, Jaclyn N. Taroni, Madeleine Ma, Kathleen Aren, Monique Hinchcliff, Kevin Tom, Mary Carns, Jennifer M. Franks, Michael L. Whitfield, Aileen Hoffmann |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Chemokine Myeloid Biopsy Cell Count Dermatology CCL2 Biochemistry Article Scleroderma 03 medical and health sciences 0302 clinical medicine Humans Medicine Myeloid Cells Longitudinal Studies Prospective Studies Molecular Biology Chemokine CCL2 Skin 030203 arthritis & rheumatology Scleroderma Systemic integumentary system biology medicine.diagnostic_test business.industry Gene Expression Profiling Monocyte Cell Biology Dendritic cell Middle Aged Mycophenolic Acid medicine.disease Gene expression profiling Treatment Outcome 030104 developmental biology medicine.anatomical_structure Case-Control Studies Immunology biology.protein Female Transcriptome business Immunosuppressive Agents |
| Zdroj: | Journal of Investigative Dermatology. 138:1301-1310 |
| ISSN: | 0022-202X |
| DOI: | 10.1016/j.jid.2018.01.006 |
| Popis: | Fewer than half of patients with systemic sclerosis demonstrate modified Rodnan skin score improvement during mycophenolate mofetil (MMF) treatment. To understand the molecular basis for this observation, we extended our prior studies and characterized molecular and cellular changes in skin biopsies from subjects with systemic sclerosis treated with MMF. Eleven subjects completed ≥24 months of MMF therapy. Two distinct skin gene expression trajectories were observed across six of these subjects. Three of the six subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in CCL2 mRNA expression in skin and reduced numbers of macrophages and myeloid dendritic cells in skin biopsies. MMF cessation at 24 months resulted in an increased inflammatory score, increased CCL2 mRNA and protein levels, modified Rodnan skin score rebound, and increased numbers of skin myeloid cells in these subjects. In contrast, three other subjects remained on MMF >24 months and showed a persistent decrease in inflammatory score, decreasing or stable modified Rodnan skin score, CCL2 mRNA reductions, sera CCL2 protein levels trending downward, reduction in monocyte migration, and no increase in skin myeloid cell numbers. These data summarize molecular changes during MMF therapy that suggest reduction of innate immune cell numbers, possibly by attenuating expression of chemokines, including CCL2. |
| Databáze: | OpenAIRE |
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