{
  "abstract": "Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic {beta}-cells. While anti-CD3 therapy can delay disease progression and preserve residual {beta}-cell function, disease reversal will likely require both immune modulation and {beta}-cell regeneration. We found that the combination of harmine and exendin-4 (H+E) reduced inflammation-induced human {beta}-cell apoptosis, suppressed cytokine signaling and immunogenicity pathways, and improved {beta}-cell function. Although H+E alone did not reverse diabetes in NOD mice, low-dose anti-CD3 followed by H+E normalized blood glucose, increased insulin levels, improved glucose tolerance, expanded {beta}-cell mass, and enhanced diabetes remission. These effects were associated with reduced pro-inflammatory T-cell responses, increased regulatory T cells, and greater expression of exhaustion-related T-cell markers, without broad lymphocyte depletion. Similar immunomodulatory effects were observed in activated human PBMCs. Transcriptomic analyses identified the lncRNA SNHG6 as a key mediator of H+E action; SNHG6 protected {beta}-cells from cytokine-induced stress, apoptosis, and immunogenicity. Together, these findings demonstrate that H+E promotes {beta}-cell recovery and resilience while reducing {beta}-cell immunogenicity, enabling remission of recent-onset T1D when combined with anti-CD3 therapy. SNHG6 emerges as a novel regulator of {beta}-cell protection during inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "City of Hope"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "G. Lu"
    },
    {
      "name": "R. Kang"
    },
    {
      "name": "M. Varela"
    },
    {
      "name": "E. Oh"
    },
    {
      "name": "Y. Li"
    },
    {
      "name": "J. Lee"
    },
    {
      "name": "L. Kebrom"
    },
    {
      "name": "J. Aldaco"
    },
    {
      "name": "J. Zhang"
    },
    {
      "name": "M. Wichman"
    },
    {
      "name": "M. Li"
    },
    {
      "name": "F. Kandeel"
    },
    {
      "name": "M. Qi"
    },
    {
      "name": "P. Wang"
    },
    {
      "name": "R. J. Devita"
    },
    {
      "name": "A. Pugliese"
    },
    {
      "name": "D. C. Thurmond"
    },
    {
      "name": "A. F. Stewart"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Garcia-Ocana"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5hee81wce9dj3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.753317",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753317v1.full",
  "id": "5hee81wce9dj3",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753317v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1311|Diabetes and associated disorders"
    ]
  ],
  "openalex": "W7214009038",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753317v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5hee81wce9dj3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:58Z",
      "native_id": "10.64898/2026.09.21.753317",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753317v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Harmine Plus Exendin-4 Enhances Remission of Recent-Onset Type 1 Diabetes Following Anti-CD3 Therapy",
  "title_text": "Harmine Plus Exendin-4 Enhances Remission of Recent-Onset Type 1 Diabetes Following Anti-CD3 Therapy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:58Z",
  "url": "https://research.draconitic.com/paper/5hee81wce9dj3",
  "venue": "bioRxiv",
  "versions": []
}