Hanlon Niamh, Gillan Natalie, Neil James, Seidler Karin
CNELM (Centre for Nutrition Education and Lifestyle Management), 14 Rectory Road, Wokingham, Berkshire RG40 1DH, UK.
Clin Nutr. 2024 Jun;43(6):1199-1215. doi: 10.1016/j.clnu.2024.04.008. Epub 2024 Apr 8.
Dysbiosis is emerging as a potential trigger of systemic lupus erythematosus (SLE). Group 3 innate lymphoid cells (ILC3s) are recognised as key regulators of intestinal homeostasis. The aryl hydrocarbon receptor (AhR) is critical to intestinal ILC3 development and function. This mechanistic review aimed to investigate whether AhR activation of gut ILC3s facilitates IL-22-mediated antimicrobial peptide (AMP) production to enhance colonisation resistance and ameliorate SLE pathology associated with intestinal dysbiosis. Furthermore, nutritional AhR ligand potential to enhance pathogen resistance was explored.
This mechanistic review involved a three-tranche systematic literature search (review, mechanism, intervention) using PubMed with critical appraisal. Data was synthesised into themes and summarised in a narrative analysis.
Preclinical mechanistic data indicate that AhR modulation of intestinal ILC3s optimises pathogen resistance via IL-22-derived AMPs. Pre-clinical research is required to validate this mechanism in SLE. Data on systemic immune consequences of AhR modulation in lupus suggest UVB-activated ligands induce aberrant AhR signalling while many dietary ligands exert beneficial effects. Data on xenobiotic-origin ligands is varied, although considerable evidence has demonstrated negative effects on Th17 to Treg balance. Limited human evidence supports the role of nutritional AhR ligands in modulating SLE pathology. Preclinical and clinical data support anti-inflammatory effects of dietary AhR ligands.
Current evidence is insufficient to fully validate the hypothesis that AhR modulation of intestinal ILC3s can enhance pathogen resistance to ameliorate lupus pathology driven by dysbiosis. However, anti-inflammatory effects of dietary AhR ligands suggest a promising role as a therapeutic intervention for SLE.
微生物群落失调正逐渐成为系统性红斑狼疮（SLE）的一个潜在触发因素。3型天然淋巴细胞（ILC3s）被认为是肠道稳态的关键调节因子。芳烃受体（AhR）对肠道ILC3的发育和功能至关重要。本机制综述旨在研究肠道ILC3s的AhR激活是否能促进IL-22介导的抗菌肽（AMP）产生，以增强定植抗性并改善与肠道微生物群落失调相关的SLE病理。此外，还探讨了营养性AhR配体增强病原体抗性的潜力。
本机制综述涉及使用PubMed进行三阶段的系统文献检索（综述、机制、干预）并进行严格评估。数据被综合成主题，并在叙述性分析中进行总结。
临床前机制数据表明，AhR对肠道ILC3s的调节通过IL-22衍生的AMPs优化病原体抗性。需要进行临床前研究以在SLE中验证这一机制。关于狼疮中AhR调节的全身免疫后果的数据表明，紫外线激活的配体诱导异常的AhR信号传导，而许多饮食配体则发挥有益作用。关于外源性配体的数据各不相同，尽管有大量证据表明其对Th17与Treg平衡有负面影响。有限的人体证据支持营养性AhR配体在调节SLE病理中的作用。临床前和临床数据支持饮食性AhR配体的抗炎作用。
目前的证据不足以充分验证肠道ILC3s的AhR调节可增强病原体抗性以改善由微生物群落失调驱动的狼疮病理这一假设。然而，饮食性AhR配体的抗炎作用表明其作为SLE的治疗干预具有广阔前景。
