脂肪不变的 NKT 细胞与表达 CD1d 的巨噬细胞相互作用以调节肥胖相关的炎症,Immunology

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脂肪不变的 NKT 细胞与表达 CD1d 的巨噬细胞相互作用以调节肥胖相关的炎症
Immunology ( IF 4.9 ) Pub Date : 2022-02-08 , DOI: 10.1111/imm.13447
Masashi Satoh _{1,

2} , Misao Iizuka ₁ , Masataka Majima _{3,

4} , Chizuru Ohwa ₂ , Akito Hattori ₂ , Luc Van Kaer ₅ , Kazuya Iwabuchi _{1,

2}

Affiliation

肥胖伴随并加速脂肪组织中的慢性炎症，尤其是内脏脂肪组织（VAT）。这种低水平的炎症使宿主容易患上代谢疾病，尤其是 2 型糖尿病。我们专注于糖脂反应性、CD1d 限制性自然杀伤 T (NKT) 细胞调节肥胖及其相关代谢后遗症的能力。我们之前报道过，CD1d 敲除 (KO) 小鼠可部分保护免受肥胖相关胰岛素抵抗的发展，这些发现在脂肪细胞特异性 CD1d 缺乏的小鼠中得到了概括，这表明 NKT 细胞-脂肪细胞相互作用在肥胖相关的胰岛素抵抗中起关键作用。加重病情。然而，许多其他表达 CD1d 的细胞有助于 NKT 细胞对脂质抗原的体内反应。^f^/^f小鼠，其中 CD1d1 基因以 Mφ 特异性方式被破坏。出乎意料的是，这些动物在 VAT 中含有更高频率的 T-bet⁺ CD4⁺ T 细胞，同时增加的 Th1 细胞因子的产生加剧了 VAT 炎症。来自突变小鼠的 Mφ 显示 IL-12p40 的产生增加，表明 M1 极化。这些发现表明 Mφ 上的 CD1d 与 NKT 细胞的相互作用在肥胖相关的增值税炎症和胰岛素抵抗中发挥有益作用，这与 CD1d 在另一种抗原呈递细胞树突状细胞中的加重作用形成鲜明对比。

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Adipose invariant NKT cells interact with CD1d-expressing macrophages to regulate obesity-related inflammation

Obesity is accompanied by and accelerated with chronic inflammation in adipose tissue, especially visceral adipose tissue (VAT). This low-level inflammation predisposes the host to the development of metabolic disease, most notably type 2 diabetes. We have focused on the capacity of glycolipid-reactive, CD1d-restricted natural killer T (NKT) cells to modulate obesity and its associated metabolic sequelae. We previously reported that CD1d knockout (KO) mice are partially protected against the development of obesity-associated insulin resistance, and these findings were recapitulated in mice with an adipocyte-specific CD1d deficiency, suggesting that NKT cell–adipocyte interactions play a critical role in exacerbating disease. However, many other CD1d-expressing cells contribute to the in vivo responses of NKT cells to lipid antigens. In the present study, we examined the role of CD1d expression by macrophages (Mϕ) in the development of obesity-associated metabolic inflammation using LysMcre-cd1d1^f^/^f mice where the CD1d1 gene is disrupted in a Mϕ-specific manner. Unexpectedly, these animals contained a higher frequency of T-bet⁺ CD4⁺ T cells in VAT with increased production of Th1 cytokines that aggravated VAT inflammation. Mϕ from mutant mice displayed increased production of IL-12p40, suggesting M1 polarization. These findings indicate that interactions of CD1d on Mϕ with NKT cells play a beneficial role in obesity-associated VAT inflammation and insulin resistance with a sharp contrast to an aggravating role of CD1d in another type of antigen-presenting cell, dendritic cells.

更新日期：2022-02-08

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