Differential Leukocyte miRNA Responses Following Pan T Cell, Allorecognition and Allosecretome-Based Therapeutics Activation
Bibliographic record
Abstract
Abstract Background: Effective immunomodulation of T cell responses is critical in treating both autoimmune diseases and cancer. Our previous studies have demonstrated that nanoscale bioengineering of cell surfaces with methoxypolyethylene glycol (mPEG) induces a potent tolerogenic immunomodulatory effect. Moreover, secretomes derived from mPEG- or control mixed lymphocyte alloactivation assays also exerted potent immunomodulatory activity that was mediated by microRNAs (miRNA). In this study, the immunomodulatory effects of Pan T cell activators (PHA and anti-CD3/CD28), alloactivation (MHC-disparate donors; ± mPEG grafting) and biomanufactured miRNA-based allo-secretome therapeutics (SYN, TA1, IA1 and IA2) were examined on T cell proliferation, subset differentiation and leukocyte miRNA expression profiles of resting human PBMC. Results: In contrast to Pan T cell activation, allorecognition and the pro-inflammatory IA1 secretome product induced increasingly controlled proliferation of resting PBMC. The differential effects of the activation strategies were also apparent in T cell differentiation and the Teff:Treg ratio and in the miRNA expression profiles noted in the treated PBMC. In contrast, the mPEG-PBMC and TA1 secretome products inhibited alloproliferation. Importantly, the activation strategies exerted significantly different miRNA expression in the treated leukocytes that was associated with differences in proliferation and cellular differentiation. Conclusions: Immunomodulatory secretome-derived, miRNA-enriched, therapeutics can be reproducibly biomanufactured that will induce the specific bioregulatory events necessary to induce the differentiation of naïve T cells to produce a tolerogeneic (TA1) or inflammatory (IA1) response both in vitro and in vivo . The successful development and biomanufacturing of immunomodulatory, miRNA-enriched, secretome biotherapeutics may provide potent tools for the systemic treatment of autoimmune diseases or enhancing the endogenous immune response to cancer while reducing the potential adverse risks of more non-specific immunomodulatory approaches.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".