Implications of a 'Third Signal' in NK Cells.

Implications of a 'Third Signal' in NK Cells.
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NK细胞中“第三信号”的含义。

DOI:
10.3390/cells10081955
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发表时间:
2021-07-31
期刊:
影响因子:
6
通讯作者:
Malarkannan S
Malarkannan S
中科院分区:
生物学2区
文献类型:
--
作者:
Khalil M;Wang D;Hashemi E;Terhune SS;Malarkannan S

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先天免疫系统和适应性免疫系统在进化上是不同的。T和B细胞中的初级信号传导依赖于体细胞重排的克隆型受体。相比之下,NK细胞使用种系编码的非克隆型受体,如NCR,NKG 2D和Ly 49 H。T和B细胞的增殖和效应子功能由MHC或可溶性体液抗原上呈递的独特肽表位决定。然而,在NK细胞中,主要信号由自身或病毒蛋白介导。由各种细胞因子介导的次级信号传导参与先天性和适应性淋巴细胞中的代谢重编程、增殖、终末成熟或记忆形成。常见的γ(γc)细胞因子受体家族,包括IL-2 R α/β/γ、IL-7 R α/γ、IL-15 R α/β/γ和IL-21 R α/γ是这些次级信号的主要实例。一组不同的细胞因子受体介导“第三”组信号传导。这些包括IL-12 R β1/β2、IL-18 R α/β、IL-23 R、IL-27 R(WSX-1/gp 130)、IL-35 R(IL-12 R β2/gp 130)和IL-39 R(IL-23 R α/gp 130),它们可以引发、激活和介导淋巴细胞中的效应子功能。在先天性和适应性淋巴细胞中,“第三”信号的存在是已知的。然而,这个“第三信号”在NK细胞中的必要性,背景和功能相关性是难以捉摸的。在这里,我们定义了当前的模式,在NK细胞的“第三”信号,并列举其临床意义。
Innate and adaptive immune systems are evolutionarily divergent. Primary signaling in T and B cells depends on somatically rearranged clonotypic receptors. In contrast, NK cells use germline-encoded non-clonotypic receptors such as NCRs, NKG2D, and Ly49H. Proliferation and effector functions of T and B cells are dictated by unique peptide epitopes presented on MHC or soluble humoral antigens. However, in NK cells, the primary signals are mediated by self or viral proteins. Secondary signaling mediated by various cytokines is involved in metabolic reprogramming, proliferation, terminal maturation, or memory formation in both innate and adaptive lymphocytes. The family of common gamma (γc) cytokine receptors, including IL-2Rα/β/γ, IL-7Rα/γ, IL-15Rα/β/γ, and IL-21Rα/γ are the prime examples of these secondary signals. A distinct set of cytokine receptors mediate a ‘third’ set of signaling. These include IL-12Rβ1/β2, IL-18Rα/β, IL-23R, IL-27R (WSX-1/gp130), IL-35R (IL-12Rβ2/gp130), and IL-39R (IL-23Rα/gp130) that can prime, activate, and mediate effector functions in lymphocytes. The existence of the ‘third’ signal is known in both innate and adaptive lymphocytes. However, the necessity, context, and functional relevance of this ‘third signal’ in NK cells are elusive. Here, we define the current paradigm of the ‘third’ signal in NK cells and enumerate its clinical implications.
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