Objective: Adoptive 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.
Methods: We 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.
Results: Deuterium 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.
Conclusion: We 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447289 | PMC |
| http://dx.doi.org/10.1002/art.40737 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Titanium nanotubes modulate immunophenotyping and cytokine secretion of T cells via IL-17A: a bioinformatic analysis and experimental validation.
Front Immunol
January 2025
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Object: We aim to explore the immunomodulatory properties of T cells on different titanium nanotubes and the key immunological factors involved in this process.
Methods: Transcriptome data from GEO database of healthy people and healthy implants were used to analyze cell infiltration and factor distribution of adaptive immune using bioinformatics tools. T cells from activated rat were cultured on titanium nanotubes that were prepared by anodization with different diameters (P-0, NT15-30 nm, NT40-100 nm, NT70-200 nm).
Tertiary lymphoid structures in colorectal cancer - organization and immune cell interactions.
Am J Clin Exp Immunol
December 2024
Department of Surgery, Medical Faculty, Trakia University Stara Zagora, Bulgria.
Tertiary lymphoid structures (TLS), formerly recognized as Crohn's-like structures, serve as crucial biomarkers for evaluating the progression of colorectal cancer (CRC). Understanding their spatial distribution, cellular composition, and interactions within CRC is paramount for comprehending the immune response in the tumor microenvironment (TME). TLS are comprised of a T-cellular compartment and a B-cellular compartment, the latter encompassing follicular dendritic cells (FDCs), high endothelial venules (HEVs), and lymphatic vessels.
View Article and Find Full Text PDFMetabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer.
Commun Biol
January 2025
San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele Milan, Milan, Italy.
Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in the absence of IL-2.
View Article and Find Full Text PDFFunctional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF Syndrome and reveals broad immune cell defects.
Clin Exp Immunol
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Introduction: STAT3 orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema and enteropathy over a 35-year period.
View Article and Find Full Text PDFEffective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.
Front Immunol
January 2025
Department of Antibody Engineering, Leadartis SL, Tres Cantos, Madrid, Spain.
Background: Immune checkpoint inhibitors have revolutionized cancer therapy, but many patients fail to respond or develop resistance, often due to reduced T cell activity. Costimulation via 4-1BB has emerged as a promising approach to enhance the effector function of antigen-primed T cells. Bispecific T cell-engaging (TCE) antibodies are an effective way to provide tumor-specific T cell receptor-mediated signaling to tumor-infiltrating lymphocytes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!