Adipose invariant NKT cells interact with CD1d‐expressing macrophages to regulate obesity‐related inflammation
Adipose invariant NKT cells interact with CD1d‐expressing macrophages to regulate obesity‐related inflammation
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DOI：
10.1111/imm.13447
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发表时间：
2022-02
期刊：
影响因子：
6.4
通讯作者：
M. Satoh;Misao Iizuka;Masataka Majima;Chizuru Ohwa;A. Hattori;L. Van Kaer;K. Iwabuchi
中科院分区：
文献类型：
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作者：
M. Satoh;Misao Iizuka;Masataka Majima;Chizuru Ohwa;A. Hattori;L. Van Kaer;K. Iwabuchi
肥胖伴随和加速了脂肪组织的慢性炎症，尤其是内脏脂肪组织(VAT)。这种低水平的炎症使宿主易于发展为代谢性疾病，最明显的是2型糖尿病。我们主要关注糖脂反应性、CD1d限制性的自然杀伤T细胞(NKT)调节肥胖及其相关代谢后遗症的能力。我们之前曾报道，CD1d基因敲除(KO)小鼠可以部分保护肥胖相关的胰岛素抵抗的发展，这些发现在脂肪细胞特异性CD1d缺乏的小鼠中重复，表明NKT细胞-脂肪细胞相互作用在疾病恶化中发挥关键作用。然而，许多其他表达CD1d的细胞参与了NKT细胞对脂类抗原的体内反应。在本研究中，我们利用LysMcRe-cd1d1f/f小鼠研究了巨噬细胞(Mϕ)CD1d表达在肥胖相关代谢性炎症发展中的作用，其中CD1d1基因以Mϕ特异性的方式被破坏。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，并增加了Th1细胞因子的产生，从而加剧了VAT的炎症。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VAT炎症和胰岛素抵抗中发挥了有利的作用，而在另一种类型的抗原呈递细胞-树突状细胞中CD1d的作用则加剧。
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‐cd1d1f/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.