Zhao Yuxin, Jiang Shan, Lv Yang, Gao Jingtao, Zhang Lichen, Tian Xueqin, Sheng Xiaohang, Wang Han, Guo Cun, Lu Wei, Li Chuang, Chang Tingmin, Lou Yunwei, Wang Hui
School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, China.
Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang, Henan, China.
J Immunol. 2025 Jun 1;214(6):1344-1357. doi: 10.1093/jimmun/vkaf021.
Although the importance of the unique member of S100 EF-hand family, S100A10 in health and disease is well appreciated, a precise characterization of S100A10 expression still remains elusive. To this purpose, we generated a knock-in mouse line in which downstream of the coding sequence of the S100a10 gene was inserted IRES-mCherry-pA sequence. Interestingly, mCherry fluorescence was widely distributed in splenic myeloid and lymphoid cells, whereas neutrophils showed a negligible mCherry level. By taking advantage of these reporter mice, we found Ly6C+ monocytes expressed the highest levels of S100A10 and bound significantly more plasminogen compared with the other respective leukocyte subsets. Furthermore, we demonstrated that S100A10 was required for emigration of Ly6C+ monocytes from bone marrow by mainly affecting CCR2 cell surface presentation. S100a10-/- mice had fewer circulating Ly6C+ monocytes and, after challenged with thioglycolate, accumulated less CCR2+ monocytes in bone marrow. However, S100A10 was not necessary for efficient neutrophil recruitment from the blood to inflamed tissue. These findings provide evidence that S100A10 is critical for monocyte mobilization and suggest its differential regulatory roles for monocyte and neutrophil chemoattractants in leukocyte homeostasis. Thus, targeting the S100A10-CCR2 pathway may be an attractive approach to regulate inflammatory responses and infectious diseases.
尽管S100 EF手蛋白家族的独特成员S100A10在健康和疾病中的重要性已得到充分认识，但对S100A10表达的精确表征仍然难以捉摸。为此，我们构建了一个敲入小鼠品系，其中在S100a10基因的编码序列下游插入了IRES-mCherry-pA序列。有趣的是，mCherry荧光广泛分布于脾脏的髓样细胞和淋巴细胞中，而中性粒细胞的mCherry水平可忽略不计。利用这些报告基因小鼠，我们发现Ly6C+单核细胞表达的S100A10水平最高，与其他各自的白细胞亚群相比，其结合的纤溶酶原明显更多。此外，我们证明S100A10是Ly6C+单核细胞从骨髓迁出所必需的，主要通过影响CCR2细胞表面表达来实现。S100a10-/-小鼠循环中的Ly6C+单核细胞较少，在用巯基乙酸刺激后，骨髓中积累的CCR2+单核细胞也较少。然而，S100A10对于从血液中有效募集中性粒细胞到炎症组织并非必需。这些发现提供了证据表明S100A10对单核细胞动员至关重要，并提示其在白细胞稳态中对单核细胞和中性粒细胞趋化因子具有不同的调节作用。因此，靶向S100A10-CCR2途径可能是调节炎症反应和感染性疾病的一种有吸引力的方法。
