{"id":535,"title":"Active immunotherapy against IL-1β restores tissue repair under chronic inflammation","title_zh":"靶向IL-1β的主动免疫治疗在慢性炎症下恢复组织修复","url":"https://doi.org/10.1073/pnas.2609135123","doi":"10.1073/pnas.2609135123","pmid":null,"journal":"Proceedings of the National Academy of Sciences","kind":"paper","lang":"en","published_at":"2026-11-02T00:00:00+00:00","fetched_at":"2026-11-08T03:45:22+00:00","authors":["Pablo Cordero-Alvarado","Natalie Kley","Eleanor L. P. Caston","Alejandra Suarez-Arnedo","Shamitha Shetty","Sophia Zhang","Tatiana Segura","Joel H. Collier"],"primary_topic":"repro-immunology","topics":[{"slug":"repro-immunology","score":5.0,"hits":["immunotherapy","macrophage"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":58.0,"final_score":64.0,"score_dims":{"novelty":72,"rigor":70,"impact":40,"relevance":15,"translation":35},"recommend_reason":"主动免疫调控IL-1β并重塑巨噬细胞极化的思路较新，对理解炎症-修复转换有参考价值；但研究对象为慢性皮肤伤口，与生殖、胚胎及ART场景关联很弱，仅对生殖免疫中炎症微环境研究有间接启发。","keywords":["IL-1β","主动免疫治疗","巨噬细胞极化","慢性炎症","组织修复","自组装肽纳米纤维"],"selected":1,"story_id":170,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-cns","source_name":"Crossref · CNS 与大子刊新上线（领域过滤）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"pnas","journal_tier":"general-top","journal_if":9.4,"is_mock":false,"summary_zh":"慢性炎症中持续存在的IL-1β信号会阻断组织修复的消退期。作者利用自组装肽纳米纤维Coil29构建抗IL-1β主动免疫疗法，在野生型与糖尿病小鼠中诱导出强而特异的IL-1β靶向免疫应答，且不引起全身免疫抑制。在慢性伤口模型中，该疗法加快上皮再形成、改善整体再生，效果优于抗IL-1β单克隆抗体；机制上抑制巨噬细胞活性、促使其向M2样极化、增强促愈合因子分泌，并在损伤部位富集抗IL-1β抗体；体外实验显示免疫小鼠血清抗体可将M1巨噬细胞重编程为M2样表型。","summary":"Chronic inflammation driven by sustained interleukin-1 beta (IL-1β) signaling disrupts the resolution phase of tissue repair by orchestrating dysregulated immune activity. As a key upstream mediator, IL-1β prolongs the activation of pro-inflammatory myeloid cells and establishes an environment that prevents the transition to tissue repair. Here, we developed an active immunotherapy against IL-1β using the self-assembling peptide nanofiber Coil29, which elicits robust and specific IL-1β-targeted immune responses in both wild-type and diabetic mice, without inducing systemic immunosuppression. In a chronic wound model, the therapy accelerated re-epithelialization and enhanced overall tissue regeneration, outperforming anti-IL-1β monoclonal antibodies. This therapy suppressed macrophage activity, promoted their M2-like polarization, enhanced pro-healing cytokine secretion and enriched the injury site with anti-IL-1β antibodies. In vitro, we found that antibodies from immunized mice reprogrammed M1 macrophages toward an M2-like phenotype, suggesting that antibody-mediated modulation of IL-1β activity may drive the enhanced wound re-epithelization seen in immunized animals. Altogether, these findings highlight a targeted, regenerative therapy for the healing of chronic wounds.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}