Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Rheumatology, Mayo Clinic, Rochester, MN 55905, USA.
Sci Adv. 2023 Sep;9(35):eadg1129. doi: 10.1126/sciadv.adg1129. Epub 2023 Sep 1.
Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of abundance on RA severity. Naïve mice gavaged with produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of . Expansion of increased CXCL5 and CD4 T cells, and both interleukin-17- and interferon-γ-producing B cells. Further, gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.
虽然类风湿关节炎 (RA) 的病因尚不清楚，但有强有力的遗传易感性和症状出现前的临床前抗体存在的证据。 在 RA 中， 扩增与严重疾病相关。在这里，我们使用胶原诱导性关节炎的人源化小鼠模型，确定了 丰度对 RA 严重程度的影响。用 灌胃的幼稚小鼠产生临床前类风湿因子，并且当诱导关节炎时，会发展为严重疾病。雌性小鼠的抗体反应更高，并且在 RA 患者中，女性的 平均负荷更高。 的扩增增加了 CXCL5 和 CD4 T 细胞，以及产生白细胞介素-17 和干扰素-γ的 B 细胞。此外， 灌胃导致肠道菌群失调和氨基酸和烟酰胺腺嘌呤二核苷酸减少，而微生物依赖性胆汁酸和琥珀酰肉碱增加导致全身性衰老样炎症。
