One standardseparate promising findings from demonstrated outcomes
START HERE
Five questions, connected—not a five-part cure
Our objective is durable gluten-specific immune control together with preserved or restored intestinal function. The organization below is our research framework, not a proven sequence of treatments. Different questions may require different models, datasets and scientific teams.
These are original summaries of selected published findings. Publication dates identify the evidence being discussed, not the present regulatory status of a product. An experimental effect is not a treatment recommendation. Authors and institutions cited below are sources, not represented as partners or endorsers.
lnc13: a possible regulator of the response threshold
Yang-Fischer and colleagues · Nature Immunology · 2026
Published finding. In HLA-DQ8 mice, loss of the regulatory RNA lnc13 increased gluten-associated inflammatory and cytotoxic responses. The work links lnc13 to restraint of immune responsiveness, including IL-15-associated activity.
Important limit. A genetic loss-of-function experiment does not demonstrate that restoring this regulator safely reverses established human disease. The paper discusses the differences between its experimental model and complex human celiac disease.
Why it belongs here. It supplies a mechanistic basis for asking about the transition from susceptibility to injury. Our question is whether a reversible regulatory state explains that transition and can be tested without broadly suppressing immunity. Source and access scope.
Wang and colleagues · Nature · Online 2025; issue 2026
Published finding. Human intestinal M cells in organoid–T-cell experiments processed and presented gluten antigen through MHC-II. The authors also report important differences between human and mouse M-cell biology.
Important limit. Demonstrating this ability does not show that the route is indispensable in an intact intestine. Other antigen-presenting populations may contribute or compensate.
Why it belongs here. The next question is the additional benefit of interrupting this route when alternatives remain present—not merely repeating the demonstration that M cells can activate T cells. Source and access scope.
TEV-408: reported protection from intestinal injury
Teva · Phase 2a announcement · September 2, 2026
Reported finding. Teva announced reduced gluten-induced intestinal damage versus placebo in its study of an investigational anti-IL-15 antibody.
Important limit. The evidence summarized here is a company topline announcement, not our independent patient-level analysis. It does not establish lasting treatment-free tolerance, and this library does not equate an early safety statement with comprehensive safety proof.
Why it belongs here. Tissue protection matters even when it is not a cure. Our question asks what remains after an intervention has genuinely ceased acting: persistent immune change, continued protection by another mechanism, or return of the harmful response. Original sponsor report.
TAK-101: an immune signal that needs careful interpretation
Kelly and colleagues · Gastroenterology · 2021
Published finding. The Phase 2a study reported an 88% reduction in the change in a gluten-specific interferon-γ response versus placebo. Thirty-three randomized participants completed the gluten challenge.
Important limit. The reported between-group change in villus-height-to-crypt-depth ratio did not reach conventional statistical significance (p=0.08), and intraepithelial lymphocyte numbers were not different. The authors interpreted the immune findings as evidence suggesting antigen-specific tolerance; that is not the same as demonstrated lifelong, treatment-free protection.
Why it belongs here. A positive immune endpoint should be retained without upgrading every tissue endpoint to a proven benefit. The later program's outcomes must be evaluated separately rather than inferred from this early report. Published trial.
Nexvax2 / RESET CeD: keep the negative evidence visible
Tye-Din and colleagues · The Lancet Gastroenterology & Hepatology · 2023
Published finding. The randomized Phase 2 study was discontinued after its planned interim analysis. Nexvax2 did not reduce the acute gluten-induced gastrointestinal symptoms assessed by the study.
Important limit. This negative result applies to the product, population, regimen and endpoints studied. It does not prove that every antigen-specific approach is ineffective. Nor is it a head-to-head comparison with TAK-101, which used a different primary endpoint.
Why it belongs here. A credible tolerance program must explain which response it aims to change and show a meaningful downstream outcome. The failure is a design lesson, not an inconvenient result to omit. Terminated-trial publication.
Gluten-reactive cell lineages can persist for decades
Risnes and colleagues · Journal of Clinical Investigation · 2018
Published finding. Researchers followed gluten-specific CD4 T-cell repertoires and found persistent clonotypes, with recall responses largely drawing on established lineages. A historical-sample subset supported persistence over decades.
Important limit. A persistent lineage is not proof that an individual cell lived for that entire period. This study does not require a future therapy to eliminate every gluten-recognizing cell.
Why it belongs here. Our interpretation is that a brief reduction in tissue injury cannot, by itself, establish control over the body's longer-lived immune memory. Functional reprogramming, selective depletion and tissue protection are different possible mechanisms that must not be conflated. Primary study.
Published finding. Biopsy-derived air–liquid interface organoids retained intestinal epithelium, supporting tissue and several immune populations. The study reproduced gluten-dependent injury and identified IL-7 activity in this experimental setting.
Important limit. These are laboratory findings, not demonstrated IL-7 treatment efficacy in patients. Long-lived epithelial growth is also not proof that the relevant immune response remains functional for an equally long period.
Why it belongs here. This is a concrete model to evaluate for injury and protection questions. Our proposed persistence comparison first needs a time-matched untreated model that still responds meaningfully; otherwise, a fading culture could resemble successful treatment. Publication · Model and dataset guide.
Wulczynski and colleagues · Nature Communications · 2026
Published finding. Human celiac samples showed altered small-intestinal microbial fiber metabolism. In sensitized mice, a dietary intervention during a gluten-free recovery period supported microbial metabolism and faster mucosal healing.
Important limit. Human observations and mouse intervention results are different evidence types. This does not establish a microbiome cure or treatment-free tolerance in people. A post-exposure recovery intervention is already part of the published design; we do not claim to have originated that idea.
Why it belongs here. Our refined question is whether an added benefit reflects tissue repair, reduced continuing immune injury during recovery, or both—and whether it persists. This is not a recommendation to take fiber supplements. Primary study.
LEARNING FROM WHAT DID NOT WORK
Negative findings and missing results are different
A published negative result
RESET CeD provides an answer to its studied symptom question: the intervention did not improve that endpoint. Retaining that result helps prevent a new proposal from ignoring a test that has already been performed. It does not justify dismissing an entire biological strategy. Read the primary evidence.
An unresolved result
An unlocated result is not evidence of benefit or failure. For a completed, delayed or discontinued program, our review method is to reconcile the registry record, publication, sponsor statement and dates; record what is actually missing; and keep the outcome unresolved until evidence supports a conclusion. This is a method, not an allegation of concealment.
Historical success is not current-program status. The early TAK-101 paper cannot answer what a later trial found. Its separate study record NCT04530123 is provided for checking the later trial. This page does not certify its current recruitment or results-posting status. Different study identifiers, populations and endpoints must stay distinct.
Our comparison rule. A statistically significant change within one group and a nonsignificant change within another do not themselves prove that the groups differ. Read the actual between-group comparison, endpoint and follow-up period. This is why the positive immune finding and uncertain tissue comparison in the 2021 TAK-101 report are both retained.
RESOURCES FOR RESEARCHERS
Choose a model that can answer the question
The resources below belong to the cited investigators and repositories. Links do not establish our access to biological material, permission to redistribute it, a laboratory partnership or a completed replication. A model's scope is as important as its sophistication.
Model suitability: published capabilities and our interpretation of the limits
Resource
Useful starting question
Limit that must remain visible
Human M-cell organoids
Antigen processing and presentation to T cells.
Presentation capability does not establish necessity in a system with other presenting cells. Wang et al.
Immune–epithelial ALI organoids
Gluten-peptide-triggered injury and downstream immune interactions.
Wang's discussion notes that the Santos model lacks M cells and uses modified gliadin peptide; it is not automatically an M-cell necessity test. Discussion · Model paper
Longitudinal human immune samples
Persistence and recall of antigen-reactive lineages.
Repertoire persistence is not an intervention trial or proof of tissue protection. Risnes et al.
Dataset spotlight: GSE200075
The Santos paper links this public single-cell dataset. Our inspection of its deposited sample descriptions identified 30 library records associated with six donor labels, including gene-expression and immune-receptor measurements from shared material—not 30 independent patients. Four donors have potential exposure/control contrasts, with control wording and cell-selection differences that require care. This is our metadata assessment, not a gene-expression reanalysis or criticism of every experiment in the paper. Open the deposited dataset.
The deposited organoid comparison is two days after stimulation, not a post-withdrawal recovery series. Cells captured by different selection methods cannot simply be treated as equivalent samples of the whole intestine. We have not calculated a pathway ranking, drug response or cure prediction from its expression matrices.
Additional deposited resources
Wang and colleagues identify GSE275771 and GSE275772. These are data pointers, not claims that we have analyzed every file. Before reuse, check the exact sample mapping, quality, associated publication, applicable terms and fit to the proposed question.
PROMISE VERSUS PROOF
What would make a stronger result?
This is our framework for interpreting the five questions—not a validated scoring system, clinical definition or prescribed experimental protocol. No single item below establishes a cure on its own.
Relevant immune function
Measure the gluten-specific response, not just a general reduction in inflammation. A quiet model with missing or failing immune cells can be misleading.
Independent tissue outcomes
Connect the proposed immune change to intestinal structure or function. A better blood measurement is not automatically restored tissue.
Persistence after withdrawal
Establish that the intervention has genuinely ceased acting and comparison cultures remain responsive. Residual drug activity is not an off-treatment result.
Selective rather than broad effects
Distinguish functional reprogramming, selective loss of pathogenic lineages and nonspecific immune suppression. Do not impose elimination of every gluten-reactive cell as an invented universal requirement.
Independent replication
Count donors and biological units correctly. Many cells or repeat measurements from the same source do not create a large independent patient study.
A result that can be challenged
State what would weaken the hypothesis, preserve contrary evidence and use a simpler explanation when it fits just as well. Report uncertainty instead of hiding it behind a single score.
These interpretation questions draw on the limitations of the studies above, especially the distinct endpoints in TAK-101, the organoid model's scope and the human immune-memory evidence. They remain open to scientific criticism.
A short guide to the terminology
Organoid
A laboratory-grown tissue model. What it represents depends on which cell types and functions it retains.
Antigen presentation
Displaying a protein fragment to immune cells. Showing that one cell type can do this does not show that it is the only route.
Immune tolerance
In this research agenda, selective control of the harmful gluten response—not simply reducing every immune response.
Clonotype
A lineage distinguished by its immune-receptor sequence. It is not interchangeable with one individual cell.
Washout / withdrawal
Removing an intervention and establishing that meaningful residual activity does not explain an apparent lasting effect.
Falsifier
An observation that would make us reject or narrow a proposed explanation. Each of the five questions includes one.
MAKE THE NEXT RESPONSE USEFUL
Criticism is a contribution
A short, specific response is more useful than a general endorsement. Identify the question number, the exact claim you disagree with, a relevant paper or dataset, and the comparison that would resolve the uncertainty. A reference showing that a question is already answered is valuable too.
Researchers who received an invitation can reply to the original email; a full review or meeting is not required. A model or dataset suggestion does not create an obligation to provide materials or perform work. Please do not send patient-identifiable records, confidential proposals or unpublished third-party material.
We do not list people who receive an email as collaborators. A reply is not permission to publish private correspondence or claim institutional endorsement. Formal studies, material transfers, funding and data-use agreements would require separate decisions by the actual responsible parties.
Public: the five-question discussion brief and this supporting evidence library. Analysis preparation: selected source-number checks and a deposited sample-design review. Not established by these outputs: an independently replicated biological result, a validated therapy, a laboratory agreement to test the proposals or demonstrated patient benefit.
The source-number checks were descriptive arithmetic, not an independent clinical trial. Metadata inspection establishes what a dataset appears to contain; it does not substitute for analyzing its expression data. Research questions and interpretations here are AI-GENERATED / UNTESTED / NOT NOVELTY-CLEARED.
This public education and scientific-discussion effort is separate from any grant application. A funding deadline does not define when the research mission ends.
Version record
— Library version 1.0: eight study/report guides, negative-evidence discussion, model/data directory and reading criteria added around the existing five-question brief. This date records editorial work, not new laboratory findings.
FOLLOW THE EVIDENCE
Sources and review scope
This is a curated starting library, not an exhaustive or systematic review, medical guideline, full trial-pipeline tracker or complete raw-data audit. Source coverage includes accessible primary abstracts, article text, selected legends and the specifically described source-data/metadata checks. Source links were reviewed September 23, 2026; not every linked full text or supplemental file was obtained.
Published results belong to the cited investigators. The connecting research questions, model-suitability judgments and reading framework are our AI-assisted interpretation. We do not reproduce third-party figures, full papers, original datasets, private correspondence or protected implementation details. Access to a public record does not certify every possible reuse right.
Accessible article, methods and published Figure 3. Its linked source table was not obtained in our review; no new statistical reanalysis is claimed.
Dataset and registry links appear beside their relevant discussions. Publication and data availability are not evidence of affiliation, funding, treatment access or an invitation for self-experimentation.