TIM-4 is expressed on invariant NKT cells but dispensable for their development and function.
TIM-4 is expressed on invariant NKT cells but dispensable for their development and function.
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DOI：
10.18632/oncotarget.12153
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Mi QS
中科院分区：
文献类型：
--
作者：
Zhang X;Gu J;Zhou L;Mi QS
T细胞免疫球蛋白和粘蛋白-4（TIM-4）主要表达于抗原呈递细胞，在免疫调节中起着多方面的作用。CD 1d限制性不变自然杀伤T（iNKT）细胞是参与多种免疫应答的强效细胞。最近报道，单独的重组TIM-4（rTIM-4）增强NKT杂交瘤DN32.D3细胞中细胞因子的产生。因此，我们假设TIM-4可能调节iNKT细胞生物学，特别是它们的细胞因子分泌功能。我们首次发现TIM-4在胸腺iNKT细胞中表达，并且在iNKT细胞迁移到次级淋巴器官，特别是在淋巴结中时，其表达增加。使用TIM-4缺陷小鼠，我们发现缺乏TIM-4不会干扰iNKT细胞发育、成熟、外周稳态和细胞因子分泌。此外，TIM-4缺乏并不改变iNKT亚系的极化，包括NKT 1、NKT 2和NKT 17。最后，混合骨髓转移实验进一步证实了来自TIM-4缺陷骨髓的正常iNKT细胞发育和功能。总之，我们的数据表明TIM-4在iNKT细胞上表达，但与它们的发育和功能无关。
T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes. Using TIM-4-deficient mice, we found that lack of TIM-4 did not disturb iNKT cell development, maturation, peripheral homeostasis and cytokine secretion. Moreover, TIM-4 deficiency did not alter the polarization of iNKT sublineages, including NKT1, NKT2 and NKT17. Finally, the mixed bone marrow transfer experiments further confirmed normal iNKT cell development and function from TIM-4-deficient bone marrow. In conclusion, our data suggest that TIM-4 is expressed on iNKT cells but dispensable for their development and function.