Stem cell factor (SCF) binds to the receptor c-Kit that is expressed on a number of myeloid and lymphoid cell populations, including Type 2 innate lymphoid cells (ILC2). However the importance of the SCF/c-Kit interaction in ILC2 has not been studied. Here we investigate the role of a specific SCF isoform, SCF248, in the allergic asthmatic response and SCF/c-Kit in ILC2 activation during chronic allergy. We observed that mice treated with a monoclonal antibody specific for SCF248 attenuated the development of chronic asthmatic disease by decreasing the number of mast cells, ILC2 and eosinophils, as well as reducing the accompanying pathogenic cytokine responses. These data were supported using SCF^fl/fl-Col1-Cre-ERT mice and W/Wv mice that demonstrated the importance of the stem cell factor/c-Kit activation during chronic allergy and the accumulation of c-kit+ cells. Finally, these data demonstrate for the first time that SCF could activate ILC2 cells in vitro for the production of key allergic cytokines. Together these findings indicate that SCF is a critical cytokine involved in the activation of ILC2 that lead to more severe outcomes during chronic allergy and that the SCF248 isoform could be an important therapeutic target to control the disease progression.

干细胞因子 (SCF) 与受体 c-Kit 结合，该受体在许多骨髓和淋巴细胞群中表达，包括 2 型先天淋巴细胞 (ILC2)。然而，SCF/c-Kit 相互作用在 ILC2 中的重要性尚未得到研究。在这里，我们研究了特定 SCF 同种型 SCF248 在过敏性哮喘反应中的作用，以及 SCF/c-Kit 在慢性过敏期间 ILC2 激活中的作用。我们观察到，用 SCF248 特异性单克隆抗体治疗的小鼠通过减少肥大细胞、ILC2 和嗜酸性粒细胞的数量以及减少伴随的致病性细胞因子反应来减轻慢性哮喘病的发展。^{使用 SCF fl/fl}支持这些数据-Col1-Cre-ERT 小鼠和 W/Wv 小鼠证明了干细胞因子/c-Kit 激活在慢性过敏和 c-kit+ 细胞积累过程中的重要性。最后，这些数据首次证明 SCF 可以在体外激活 ILC2 细胞以产生关键的过敏性细胞因子。这些发现共同表明，SCF 是参与 ILC2 激活的关键细胞因子，在慢性过敏期间会导致更严重的后果，并且 SCF248 同种型可能是控制疾病进展的重要治疗靶点。