{
  "abstract": "Non-canonical IL-2 signaling, termed Monoclonal antibody or Matrix-directed Alternative Cytokine Signaling (MACS), is mediated by a CD25-chemokine receptor complex and operates in concert with the canonical JAK-STAT5 pathway; however, its role in T cell homeostasis remains poorly defined. Here, we uncover a role for MACS in regulatory T cell (Treg) differentiation and functional specification. We generated Il2E66K/E66K mice in which CD25-CCR7 assembly is disrupted and IL-2-induced STAT5 phosphorylation is preserved. Immunophenotyping analysis by flow cytometry revealed that MACS deficiency reduces the accumulation of Nrp1- Foxp3+ Tregs in gut-associated lymphoid tissues from 24-weeks-old Il2E66K/E66K mutant mice. Single-cell transcriptomics, functional suppression assays, and in vitro differentiation revealed that MACS engagement drives Treg differentiation and sustains effector Treg programs - marked by robust IL-10 expression - in part via an AP-1-dependent transcriptional network. These findings establish IL-2 MACS as a distinct signal directing peripheral immune tolerance and highlight a potential node for targeted immunomodulation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, University of California San Diego School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "A. Meecham"
    },
    {
      "name": "S. H. J. Kim"
    },
    {
      "name": "M. H. Fernandes de Lima"
    },
    {
      "name": "M. Tang"
    },
    {
      "name": "B. Liao"
    },
    {
      "name": "S. Chan"
    },
    {
      "name": "H.-s. Lee"
    },
    {
      "name": "L.-F. Lu"
    },
    {
      "name": "Z. Zhang"
    },
    {
      "name": "C. Jefferies"
    },
    {
      "name": "M. Guma"
    },
    {
      "name": "M.-A. Lopez-Ramirez"
    },
    {
      "affs": [
        0
      ],
      "name": "M. H. Ginsberg"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c5enyw3kkkrdt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.756301",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.756301v1.full",
  "id": "c5enyw3kkkrdt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.756301v1",
  "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",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7221884790",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.756301v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c5enyw3kkkrdt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:52Z",
      "native_id": "10.64898/2026.10.07.756301",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.756301v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Non-canonical IL-2 signaling facilitates peripheral regulatory T cell differentiation",
  "title_text": "Non-canonical IL-2 signaling facilitates peripheral regulatory T cell differentiation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:52Z",
  "url": "https://research.draconitic.com/paper/c5enyw3kkkrdt",
  "venue": "bioRxiv",
  "versions": []
}