Ganesan S, Luu T T, Chambers B J, Meinke S, Brodin P, Vivier E, Wetzel D M, Koleske A J, Kadri N, Höglund P
Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, Center for Infectious Medicine, F59, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Scand J Immunol. 2017 Sep;86(3):135-142. doi: 10.1111/sji.12574.
Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.
小鼠自然杀伤（NK）细胞的反应性是在一个由抑制性Ly49和NKG2A受体与MHC I类分子结合所引导的教育过程中确定的。有人提出，人类NK细胞中的抑制性信号传导涉及Abl-1（c-Abl）介导的Crk磷酸化，通过破坏包括C3G和c-Cbl在内的信号复合物来降低NK细胞功能，这表明NK细胞教育可能涉及c-Abl。在小鼠NK细胞中特异性缺乏c-Abl表达的小鼠表现出正常的抑制性和激活性受体库。此外，c-Abl缺陷的NK细胞在ITAM受体触发后正常地进行钙流，有效杀伤YAC-1肿瘤细胞，并且在激活性受体刺激后产生IFN-γ的能力正常，甚至略有升高。与这些结果一致，NK细胞中的c-Abl缺陷并不影响通过Ly49G2、Ly49A和NKG2A受体的NK细胞抑制。我们得出结论，小鼠抑制性受体下游的信号传导不涉及c-Abl，并且c-Abl在小鼠NK细胞教育中不发挥主要作用。
