Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis.
Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis.
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DOI：
10.1186/s12964-023-01133-0
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发表时间：
2023-08-03
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影响因子：
--
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Tyro3、Axl 和 Mertk（缩写为 TAM）包含同源 1 型受体酪氨酸激酶 (RTK) 家族，这些受体被认为是抑制炎症的抑制性受体，但它们在类风湿性关节炎发病机制中的作用仍未得到充分研究。在这里，为了研究炎症性关节炎模型中的 TAM，通过注射 K/BxN 血清在单个 TAM 缺陷小鼠（Tyro3-KO、Axl-KO、Mertk-KO）中诱导抗体诱导的关节炎。随后，在 WT 和 TAM 缺陷小鼠中评估关节炎症和细胞因子水平，以及 Fcγ R 和补体受体的表达。与同窝对照小鼠相比，Axl−/− 和 Mertk−/− 小鼠出现了更严重的抗体诱导关节炎，而相比之下，Tyro3−/− 小鼠表现出减轻的关节炎症。与此同时，Axl−/− 和 Mertk−/− 小鼠关节中的细胞因子水平也显着升高，而 Tyro3−/− 关节组织中的细胞因子水平下降。在分子和细胞水平上，TAM表现出不同的表达模式，其中单核细胞表达Axl和Mertk，但不表达Tyro3，而中性粒细胞表达Axl和Tyro3，但很少表达Mertk。此外，Fcγ受体和C5aR的表达与TAM的表达表现出不同的模式，其中与野生型小鼠相比，Axl−/−和Mertk−/−小鼠的单核细胞中FcγRIV较高，而Tyro3−/−中性粒细胞中FcγRI、FcγRIII和FcγRIV的表达水平较低。最后，C5aR 的表达在 Mertk−/− 单核细胞中增加，而在 Tyro3−/− 中性粒细胞中减少。这些数据表明，Axl、Mertk 和 Tyro3 在抗体诱导的关节炎中具有不同的功能，部分原因是细胞因子产生以及 FcγR 和 C5aR 表达的差异调节。视频摘要 在线版本包含可在 10.1186/s12964-023-01133-0 获取的补充材料。
Tyro3, Axl, and Mertk (abbreviated TAMs) comprise a family of homologous type 1 receptor tyrosine kinases (RTKs) that have been implicated as inhibitory receptors that dampen inflammation, but their roles in the pathogenesis of rheumatoid arthritis remains understudied. Here, to investigate TAMs in an inflammatory arthritis model, antibody-induced arthritis in single TAM-deficient mice (Tyro3- KO, Axl-KO, Mertk-KO) was induced by K/BxN serum injection. Subsequently, joint inflammation and cytokine levels, as well as the expression of Fcγ Rs and complement receptors were assessed in WT and TAM-deficient mice. Compared with littermate control mice, Axl−/− and Mertk−/− mice developed more severe antibody-induced arthritis, while in contrast, Tyro3−/− mice showed diminished joint inflammation. Concomitantly, the levels of cytokines in joints of Axl−/− and Mertk−/− mice were also significantly increased, while cytokines in the Tyro3−/− joint tissues were decreased. At the molecular and cellular level, TAMs showed distinct expression patterns, whereby monocytes expressed Axl and Mertk, but no Tyro3, while neutrophils expressed Axl and Tyro3 but little Mertk. Moreover, expression of Fcγ receptors and C5aR showed different patterns with TAMs expression, whereby FcγRIV was higher in monocytes of Axl−/− and Mertk−/− mice compared to wild-type mice, while Tyro3−/− neutrophils showed lower expression levels of FcγRI, FcγRIII and FcγRIV. Finally, expression of C5aR was increased in Mertk−/− monocytes, and was decreased in Tyro3−/− neutrophils. These data indicate that Axl, Mertk and Tyro3 have distinct functions in antibody-induced arthritis, due in part to the differential regulation of cytokines production, as well as expression of FcγRs and C5aR. Video Abstract The online version contains supplementary material available at 10.1186/s12964-023-01133-0.
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影响因子：
3.7
作者：
Paradowska-Gorycka, A.;Sowinska, A.;Olesinska, M.
通讯作者：
Olesinska, M.
影响因子：
4.4
作者：
Corr, M;Crain, B
通讯作者：
Crain, B
狼疮患者的循环树突状细胞和单核细胞中Mer酪氨酸激酶的表达增加：与血浆干扰素活性和类固醇治疗的相关性。
影响因子：
4.9
作者：
Hilliard BA;Zizzo G;Ulas M;Linan MK;Schreiter J;Cohen PL
通讯作者：
Cohen PL
DOI：
10.1073/pnas.1014515107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Nimmerjahn, Falk;Lux, Anja;Ravetch, Jeffrey V.
通讯作者：
Ravetch, Jeffrey V.
影响因子：
5.2
作者：
Nakamura, YS;Hakeda, Y;Suda, T
通讯作者：
Suda, T