Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition [scRNA-seq]

Type 2 cytokine responses promote parasitic immunity and initiate tissue repair but, can also result in immunopathologies when not properly restricted. Basophilia is recognized as a common feature of type 2 inflammation, however, the roles basophils play in regulating these responses remain unknown. Here, we demonstrate that helminth-induced ILC2 responses are exaggerated in the absence of basophils, resulting in increased inflammation and diminished lung function. Additionally, we show that ILC2s from basophil-depleted mice express reduced levels of the receptor for the neuropeptide, neuromedin B (NMB). Critically, NMB stimulation inhibited ILC2 responses from control but not basophil-depleted mice, and basophils were sufficient to directly enhance NMB receptor (NMBR) expression on ILC2s. These studies suggest that basophils prime ILC2s to respond to neuron-derived signals necessary to maintain tissue integrity. Further, these data provide mechanistic insight into the functions of basophils and identify NMB as a potent inhibitor of type 2 inflammation.

2型细胞因子应答可促进寄生虫免疫并启动组织修复，但倘若调控失当，也可引发免疫病理损伤。嗜碱性粒细胞增多（Basophilia）被认为是2型炎症的常见特征，然而嗜碱性粒细胞（basophils）在调控此类应答中的具体作用仍未明确。本研究证实，在缺失嗜碱性粒细胞的情况下，蠕虫诱导的2型固有淋巴细胞（ILC2）应答会过度活化，进而加剧炎症反应并导致肺功能减退。此外，研究发现，来自嗜碱性粒细胞清除小鼠的2型固有淋巴细胞，其神经肽神经介素B（NMB）的受体表达水平显著下调。至关重要的是，神经介素B刺激可抑制对照组小鼠的2型固有淋巴细胞应答，但对嗜碱性粒细胞清除小鼠的该应答无此抑制效果；且仅需嗜碱性粒细胞即可直接上调2型固有淋巴细胞上的神经介素B受体（NMBR）的表达。上述研究表明，嗜碱性粒细胞可致敏2型固有淋巴细胞，使其响应维持组织完整性所需的神经元源性信号。本研究进一步为嗜碱性粒细胞的功能提供了机制性见解，并确定神经介素B是2型炎症的强效抑制剂。