Bardet–Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by the dysfunction of primary cilia. The immune system of patients with ciliopathies has not been investigated. However, there are multiple indications that the impairment of the processes typically associated with cilia may have influence on the hematopoietic compartment and immunity. In this study, we analyze clinical data of BBS patients and corresponding mouse models carrying mutations in Bbs4 or Bbs18. We find that BBS patients have a higher prevalence of certain autoimmune diseases. Both BBS patients and animal models have altered red blood cell and platelet compartments, as well as elevated white blood cell levels. Some of the hematopoietic system alterations are associated with BBS‐induced obesity. Moreover, we observe that the development and homeostasis of B cells in mice is regulated by the transport complex BBSome, whose dysfunction is a common cause of BBS. The BBSome limits canonical WNT signaling and increases CXCL12 levels in bone marrow stromal cells. Taken together, our study reveals a connection between a ciliopathy and dysregulated immune and hematopoietic systems.

中文翻译：

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Bardet-Biedl 综合征纤毛病与造血功能改变和自我耐受失调有关

Bardet-Biedl 综合征 (BBS) 是一种由原发性纤毛功能障碍引起的多效性遗传病。尚未研究纤毛病患者的免疫系统。然而，有多种迹象表明，通常与纤毛相关的过程受损可能对造血区室和免疫产生影响。在这项研究中，我们分析了 BBS 患者的临床数据和携带Bbs4或Bbs18突变的相应小鼠模型. 我们发现 BBS 患者某些自身免疫性疾病的患病率较高。BBS 患者和动物模型都改变了红细胞和血小板隔室，以及升高的白细胞水平。一些造血系统改变与 BBS 引起的肥胖有关。此外，我们观察到小鼠 B 细胞的发育和稳态受转运复合物 BBSome 的调节，其功能障碍是 BBS 的常见原因。BBSome 限制了典型的 WNT 信号传导并增加了骨髓基质细胞中的 CXCL12 水平。总之，我们的研究揭示了纤毛病与失调的免疫和造血系统之间的联系。