Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.
Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.
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DOI：
10.1371/journal.pone.0095365
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tomino Y
中科院分区：
文献类型：
--
作者：
Aizawa M;Suzuki Y;Suzuki H;Pang H;Kihara M;Nakata J;Yamaji K;Horikoshi S;Tomino Y
以前的临床和实验研究表明，导致IgA肾病(IgAN)的细胞至少部分位于骨髓(BM)。事实上，我们已经证明，不仅在正常小鼠中，而且在不依赖于IgA+细胞归巢于粘膜或次级淋巴组织的再生障碍性小鼠(Aly/Aly)中，通过从有IgA肾病倾向的小鼠的骨髓移植(BMT)可以在实验中重建小鼠的IgA肾病。本研究的目的是进一步评估次级淋巴结(LN)是否有助于本病的进展。将几株IgAN易感小鼠的骨髓细胞移植到Aly/Aly和野生型小鼠(B6)体内。移植的Aly/Aly虽然表现出与B6相同程度的系膜IgA和Ig G沉积，以及相同的血清Ig A和Ig A-Ig G免疫复合物(IC)升高水平，但即使在一定程度上，肾小球损伤的进展也仅在B6观察到。Aly/Aly的这种解偶联与缺乏CD4+T细胞和巨噬细胞浸润有关，尽管两个受体的肾脏常驻细胞对肾炎IC的趋化能力是相同的。提示在肾炎性IgA和IgA/Ig G IC沉积后，IgAN的完全进展可能需要继发性LN。
Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN), at least in part, are localized in bone marrow (BM). Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT) from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly) independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN) contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6). Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC) as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.
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影响因子：
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作者：
Couzi, Lionel;Merville, Pierre;Blanco, Patrick
通讯作者：
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影响因子：
19.6
作者：
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影响因子：
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作者：
deFijter, JW;Eijgenraam, JW;Bake, AWLV
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