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Bardet–Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self‐tolerance
Author(s) -
Tsyklauri Oksana,
Niederlova Veronika,
Forsythe Elizabeth,
Prasai Avishek,
Drobek Ales,
Kasparek Petr,
Sparks Kathryn,
Trachtulec Zdenek,
Prochazka Jan,
Sedlacek Radislav,
Beales Philip,
Huranova Martina,
Stepanek Ondrej
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050785
Subject(s) - ciliopathy , ciliopathies , bardet–biedl syndrome , cilium , haematopoiesis , biology , immunology , stromal cell , immune system , wnt signaling pathway , bone marrow , stem cell , microbiology and biotechnology , signal transduction , genetics , cancer research , phenotype , gene
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.