Sensitizer-Induced Basophils Accelerate Skin Re-Epithelialization via IL-4/IL-13-Mediated Macrophage Polarization

  • Allergy. 2026 May;81(5):1487-1499. doi: 10.1111/all.70279.
Yufei Zhang  1 ,  Xueting Peng  1 ,  Kaixuan Ren  1 ,  Shiran Kang  1 ,  Zihan Xue  1 ,  Yazhuo Li  1 ,  Zhu Yan  2 ,  Rongfang Feng  1 ,  Min Gao  1 ,  Qin Chen  1 ,  Xiaoying Ning  1 ,  Fan Bai  1 ,  Liesu Meng  3  4 ,  Yumin Xia  1 ,  Yale Liu  1
Affiliations
  • 1. Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 3. National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 4. Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, China.
PMID: 41787818 DOI: 10.1111/all.70279
Abstract

Background: Atopic dermatitis (AD) patients exhibit a paradox of impaired skin barrier with intense itching, yet often demonstrate rapid re-epithelialization after scratching. While basophils are key effector cells in allergic inflammation, their role in the subsequent tissue repair remains unexplored.

Objective: We investigated whether basophils, recruited during sensitized skin responses, contribute to wound healing.

Methods: Using single-cell RNA Sequencing, flow cytometry, and immunofluorescence, we mapped basophil infiltration and activation in sensitizer (oxazolone)-induced skin injury models. We employed genetic (Mcpt8CT/+R26DTA/+) and antibody-mediated (anti-FcεRI) basophil depletion, as well as basophil-specific Il4/Il13 knockout mice (Il4/13fl/flMcpt8CT/+) to define their functional contribution. Macrophage polarization was assessed by flow cytometry, RT-qPCR, and immunohistochemistry.

Results: We identified a significant enrichment of basophils in wounded skin, peaking at day 3-6 post-injury. Sensitizer-challenge enhanced basophil recruitment and accelerated wound closure, angiogenesis, and re-epithelialization. Depletion of basophils severely impaired these repair processes. Mechanistically, basophils were the predominant source of IL-4 and IL-13 in the early wound microenvironment. These cytokines were essential for driving macrophage polarization toward a pro-repair M2 phenotype. Loss of IL4/IL13 specifically in basophils phenocopied the healing defects observed in basophil-deficient mice, and this could be rescued by local cytokine administration.

Conclusion: Our study uncovers a novel pro-repair function of basophils in sensitizer-exposed skin. Beyond their well-known role in provoking itch and inflammation, basophils are critical for initiating type 2 immune-mediated tissue regeneration via IL-4/IL-13-dependent macrophage reprogramming. This axis represents a promising therapeutic target for chronic wounds, particularly in the context of allergic skin disorders.

Keywords
IL‐4/IL‐13; basophils; macrophage M2 polarization; wound healing.
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