维生素A和D对人类固有淋巴细胞中效应细胞因子的表达和肠道归巢整合素有拮抗作用。
Vitamins A and D have antagonistic effects on expression of effector cytokines and gut-homing integrin in human innate lymphoid cells.
作者信息
Ruiter B, Patil S U, Shreffler W G
机构信息
Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
出版信息
Clin Exp Allergy. 2015 Jul;45(7):1214-25. doi: 10.1111/cea.12568.
BACKGROUND
Retinoic acid (RA), the main biologically active metabolite of vitamin A, is known to promote gut homing of lymphocytes, as well as various regulatory and effector immune responses. In contrast, the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is predominantly immunosuppressive. Little is known about the direct effects of these vitamins on the recently identified innate lymphoid cells (ILCs).
OBJECTIVE
We sought to characterize the effects of RA and 1,25D3 on human ILCs.
METHODS
Peripheral blood mononuclear cells were isolated from 27 non-selected blood donor buffy coats, and ILCs were sorted by FACS. ILC1, ILC2, and ILC3 cells were cultured for 5 days with RA, 1,25D3, and various cytokines known to activate ILCs (IL-2, IL-7, IL-12, thymic stromal lymphopoietin (TSLP), IL-25, and IL-33). Cytokines produced by ILCs were measured in culture supernatants, and surface receptor expression was analysed by flow cytometry.
RESULTS
Retinoic acid acted synergistically with IL-2 and other activating cytokines to induce expression of the gut-homing integrin α4β7 in ILCs, as well as production of IL-5 and IL-13 in ILC2 cells, and IFN-γ in ILC1 and ILC3 cells. Expression of integrin α4β7 and cytokine production in ILCs stimulated with RA + IL-2 was increased at least fourfold as compared to ILCs cultured with RA or IL-2 alone. In contrast, RA completely inhibited the IL-2-induced expression of cutaneous lymphocyte antigen (CLA) in ILCs. Moreover, addition of 1,25D3 to ILCs cultured with RA + IL-2 inhibited cytokine production and expression of integrin α4β7 by at least 30%.
CONCLUSIONS
Retinoic acid and 1,25D3 have antagonistic effects on the expression of effector cytokines and gut-homing integrin by human ILCs. The balance between these vitamins may be an important factor in the functioning of ILCs and the diseases in which ILCs are implicated, such as allergic inflammation.
背景
视黄酸（RA）是维生素A的主要生物活性代谢产物，已知其可促进淋巴细胞归巢至肠道，以及引发各种调节性和效应性免疫反应。相比之下，维生素D的活性形式1,25 - 二羟基维生素D3（1,25D3）主要具有免疫抑制作用。关于这些维生素对最近发现的固有淋巴细胞（ILC）的直接影响，人们了解甚少。
目的
我们试图明确RA和1,25D3对人ILC的影响。
方法
从27份未选择的献血者血沉棕黄层中分离外周血单个核细胞，并用荧光激活细胞分选术（FACS）分选ILC。将ILC1、ILC2和ILC3细胞与RA、1,25D3以及已知可激活ILC的各种细胞因子（IL - 2、IL - 7、IL - 12、胸腺基质淋巴细胞生成素（TSLP）、IL - 25和IL - 33）一起培养5天。在培养上清液中检测ILC产生的细胞因子，并通过流式细胞术分析表面受体表达。
结果
视黄酸与IL - 2及其他激活细胞因子协同作用，诱导ILC中肠道归巢整合素α4β7的表达，以及ILC2细胞中IL - 5和IL - 13的产生，以及ILC1和ILC3细胞中IFN - γ的产生。与单独用RA或IL - 2培养的ILC相比，用RA + IL - 2刺激的ILC中整合素α4β7的表达和细胞因子的产生增加了至少四倍。相比之下，RA完全抑制了IL - 2诱导的ILC中皮肤淋巴细胞抗原（CLA）的表达。此外，向用RA + IL - 2培养的ILC中添加1,25D3可使细胞因子产生和整合素α4β7的表达至少降低30%。
结论
视黄酸和1,25D3对人ILC效应细胞因子的表达和肠道归巢整合素具有拮抗作用。这些维生素之间的平衡可能是ILC功能以及与ILC相关疾病（如过敏性炎症）发生发展的重要因素。
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