Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus
| العنوان: | Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus |
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| المؤلفون: | Qizhi Tang, Beverly Welch, Kelly A. Remedios, Amy L. Putnam, David Wofsy, Marc K. Hellerstein, Priscila M Sandova, James McNamara, Angela P. Lares, Michael Rosenblum, Marc Fitch, Anna Haemel, Keyon Taravati, Jeffrey A. Bluestone, Maria Dall'Era, Mariela L. Pauli |
| المصدر: | Arthritis & Rheumatology. 71:431-440 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Adoptive cell transfer, medicine.medical_treatment, Immunology, Cell- and Tissue-Based Therapy, chemical and pharmacologic phenomena, Inflammation, medicine.disease_cause, Immunotherapy, Adoptive, T-Lymphocytes, Regulatory, Article, Autoimmunity, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Interferon, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Autoimmune disease, Lupus erythematosus, business.industry, hemic and immune systems, Immunotherapy, Middle Aged, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, medicine.drug |
| الوصف: | Author(s): Dall'Era, Maria; Pauli, Mariela L; Remedios, Kelly; Taravati, Keyon; Sandova, Priscila M; Putnam, Amy L; Lares, Angela; Haemel, Anna; Tang, Qizhi; Hellerstein, Marc; Fitch, Marc; McNamara, James; Welch, Beverly; Bluestone, Jeffrey A; Wofsy, David; Rosenblum, Michael D; Autoimmunity Centers of Excellence | Abstract: ObjectiveAdoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease.MethodsWe describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment.ResultsDeuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-γ pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production.ConclusionWe report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses. |
| تدمد: | 2326-5205 2326-5191 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e646dcdac814599b3cbd5055c1bc84dbTest https://doi.org/10.1002/art.40737Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e646dcdac814599b3cbd5055c1bc84db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23265205 23265191 |
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