The Unit of Proteomics and Flow Cytometry, Allergy and Clinical Immunology, Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel.
Department of Pathology, Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel.
Front Immunol. 2024 Jul 22;15:1327040. doi: 10.3389/fimmu.2024.1327040. eCollection 2024.
The proximity of activated T cells and mast cells in the lesional skin of patients with chronic spontaneous urticaria (CSU) is held to contribute to the development of wheals and angioedema. In a previous study, we demonstrated that increased IL-17 expression in T cells and mast cells in skin lesions of patients with CSU is associated with T/mast cell proximity, but the mechanisms that drive T cell/mast cell co-localization remain unknown.
To assess if chemokines expressed in lesional CSU skin contribute to T cell/mast cell proximity.
Biopsies from lesional CSU skin were compared to biopsies from healthy skin for expression of CCR5 and its ligand CCL3 by CD4 T cells and mast cells, respectively.
Numbers of CCR5-positive CD4 T cells in lesional CSU skin were significantly increased as compared to healthy normal skin (p < 0.0001). The number of mast cells expressing CCL3 (ligand for CCR5) in CSU skin was also increased (p < 0.0002) and significant association with T-cell close proximity (p < 0.0001) is noticed.
The close proximity of T cells and mast cells in the skin of severe CSU may be driven, at least in part by increased CCR5 and CCL3 expression. Therapies that target CCL3 interaction with CCR5 should be assessed for their effects in CSU.
慢性自发性荨麻疹（CSU）患者皮损处激活的 T 细胞和肥大细胞的接近被认为有助于风团和血管性水肿的发展。在之前的一项研究中，我们证明了 CSU 患者皮损中 T 细胞和肥大细胞中 IL-17 表达的增加与 T/肥大细胞的接近有关，但导致 T 细胞/肥大细胞共定位的机制尚不清楚。
评估 CSU 皮损中表达的趋化因子是否有助于 T 细胞/肥大细胞的接近。
比较 CSU 皮损和健康皮肤活检组织中 CD4 T 细胞和肥大细胞分别表达 CCR5 和其配体 CCL3 的情况。
与健康正常皮肤相比，CSU 皮损中 CCR5 阳性 CD4 T 细胞数量明显增加（p < 0.0001）。CSU 皮肤中表达 CCL3（CCR5 配体）的肥大细胞数量也增加（p < 0.0002），并与 T 细胞的密切接近显著相关（p < 0.0001）。
CSU 严重患者皮肤中 T 细胞和肥大细胞的密切接近可能至少部分是由 CCR5 和 CCL3 表达增加驱动的。应评估靶向 CCL3 与 CCR5 相互作用的疗法在 CSU 中的疗效。
