Dysregulation of mucosal immunity may play a role in the pathogenesis of IgA nephropathy (IgAN). However, it is unclear whether the nasal-associated lymphoid tissue (NALT) or gut-associated lymphatic tissue is the major induction site of nephritogenic IgA synthesis. To examine whether exogenous mucosal antigens exacerbate the pathogenesis of IgAN, we assessed the disease phenotypes of IgAN-onset ddY mice housed germ-free. These mice were transferred to a specific pathogen-free environment and divided into three groups: challenged with the Toll-like receptor 9 (TLR9) ligand CpG-oligodeoxynucleotide, fecal transplantation, and the untreated control group. The levels of aberrantly glycosylated IgA and IgG-IgA immune complexes were measured in the serum and supernatant of cultured cells purified from the NALT, mesenteric lymph nodes, and Peyer’s patch. Although the germ-free IgAN-onset ddY mice did not develop IgAN, they showed aggravation of kidney injury with mesangial IgA deposition after transfer to the specific pathogen-free state. The NALT cells produced more aberrantly glycosylated IgA than those from the mesenteric lymph node and Peyer’s patch, resulting in induction of IgG-IgA immune complexes formation. Additionally, TLR9 enhanced the production of nephritogenic IgA and IgG-IgA immune complexes by nasal-associated lymphoid but not gut-associated lymphatic cells. Furthermore, the germ-free IgAN-onset ddY mice nasally immunized with CpG-oligonucleotide showed aggravation of kidney injury with mesangial IgA deposition, whereas those that received fecal transplants did not develop IgAN. Thus, NALT is the major induction site of the production of aberrantly glycosylated IgA in murine IgAN.

黏膜免疫失调可能在 IgA 肾病 (IgAN) 的发病机制中起作用。然而，尚不清楚鼻相关淋巴组织 (NALT) 还是肠道相关淋巴组织是肾炎 IgA 合成的主要诱导位点。为了检查外源性粘膜抗原是否会加剧 IgAN 的发病机制，我们评估了无菌饲养的 IgAN 发病 ddY 小鼠的疾病表型。这些小鼠被转移到特定的无病原体环境中并分为三组：用 Toll 样受体 9 (TLR9​​) 配体 CpG-寡脱氧核苷酸攻击、粪便移植和未处理的对照组。在从 NALT、肠系膜淋巴结和 Peyer 结节纯化的培养细胞的血清和上清液中测量异常糖基化 IgA 和 IgG-IgA 免疫复合物的水平。虽然无菌 IgAN 发病的 ddY 小鼠没有发生 IgAN，但在转移到特定的无病原体状态后，它们表现出肾损伤加重，系膜 IgA 沉积。NALT 细胞产生的异常糖基化 IgA 比来自肠系膜淋巴结和 Peyer 淋巴结的 IgA 多，从而诱导 IgG-IgA 免疫复合物的形成。此外，TLR9 增强了鼻相关淋巴细胞而不是肠道相关淋巴细胞产生肾炎性 IgA 和 IgG-IgA 免疫复合物。此外，用 CpG 寡核苷酸鼻腔免疫的无菌 IgAN 发病 ddY 小鼠显示肾损伤加重并伴有系膜 IgA 沉积，而接受粪便移植的小鼠没有发生 IgAN。因此，NALT 是鼠 IgAN 中异常糖基化 IgA 产生的主要诱导位点。