Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Gronostajowa 7, 30-387 Krakow, Poland; Jagiellonian University, Doctoral School of Exact and Natural Sciences, Lojasiewicza 11, 30-348 Krakow, Poland.
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Gronostajowa 7, 30-387 Krakow, Poland.
Biochim Biophys Acta Gen Subj. 2024 Oct;1868(10):130671. doi: 10.1016/j.bbagen.2024.130671. Epub 2024 Jul 18.
The skin is a complex organ, and the intricate network between keratinocytes and immune cells is critical for ensuring skin function. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is a ribonuclease that functions as a key negative modulator of inflammation. We previously reported that conditional deletion of MCPIP1 in keratinocytes (Mcpip1) impairs skin integrity in adult mice. A similar phenotype was observed following the depletion of MCPIP1 in the myeloid compartment (Mcpip1). The aim of this study was to develop a keratinocyte and myeloid double-MCPIP1 knockout mouse model to clarify the specific roles of myeloid and epidermal MCPIP1 in skin biology. Histological analyses indicated that the skin morphology changed after depletion of MCPIP1 in cells of myeloid origin as well as in keratinocytes. The thicknesses of the epidermal and subcutaneous fat layers increased in the mice with a loss of epidermal MCPIP1, whereas the loss of myeloid MCPIP1 had the opposite effect. In addition, both types of mice showed opposite responses to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Transcriptomic profiling of whole-skin lysates revealed some common target transcripts in all the knockout mice. Further analyses revealed that distinct pathways are modulated following the loss of epidermal or myeloid MCPIP1. The skin morphology and inflammatory phenotype of keratinocyte and myeloid double-MCPIP1 knockout mice resembled those of mice with only keratinocyte-specific knockout of MCPIP1. Overall, myeloid and epidermal MCPIP1 play important but distinct roles in the modulation of skin-related processes.
皮肤是一种复杂的器官，角质形成细胞和免疫细胞之间错综复杂的网络对于确保皮肤功能至关重要。单核细胞趋化蛋白-1 诱导蛋白 1（MCPIP1）是一种核糖核酸酶，作为炎症的关键负调节剂发挥作用。我们之前报道过，角质形成细胞中 MCPIP1 的条件缺失（Mcpip1）会损害成年小鼠的皮肤完整性。在髓系细胞（Mcpip1）中耗尽 MCPIP1 时也观察到类似的表型。本研究旨在开发角质形成细胞和髓系双重 MCPIP1 敲除小鼠模型，以阐明髓系和表皮 MCPIP1 在皮肤生物学中的特定作用。组织学分析表明，在髓系起源的细胞以及角质形成细胞中耗尽 MCPIP1 后，皮肤形态发生改变。表皮 MCPIP1 缺失的小鼠表皮和皮下脂肪层厚度增加，而髓系 MCPIP1 缺失则产生相反的效果。此外，两种类型的小鼠对 12-O-十四烷酰佛波醇-13-乙酸酯的刺激均表现出相反的反应。全皮肤裂解物的转录组分析揭示了所有敲除小鼠中一些共同的靶转录物。进一步分析表明，表皮或髓系 MCPIP1 缺失后会调节不同的途径。角质形成细胞和髓系双重 MCPIP1 敲除小鼠的皮肤形态和炎症表型与仅角质形成细胞特异性敲除 MCPIP1 的小鼠相似。总体而言，髓系和表皮 MCPIP1 在调节皮肤相关过程中发挥着重要但不同的作用。
