Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance

0544158 - ÚMG 2022 RIV GB eng J - Journal Article
Tsyklauri, Oksana - Niederlová, Veronika - Forsythe, E. - Prasai, Avishek - Drobek, Aleš - Kašpárek, Petr - Sparks, K. - Trachtulec, Zdeněk - Procházka, Jan - Sedláček, Radislav - Beales, P.L. - Huranová, Martina - Štěpánek, Ondřej
Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance.
Embo Reports. Roč. 22, č. 2 (2021), č. článku e50785. ISSN 1469-221X. E-ISSN 1469-3178
R&D Projects: GA ČR(CZ) GJ17-20613Y; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:68378050
Keywords : Bardet-Biedl Syndrome * ciliopathy * cxcl12 * immunity * obesity
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 9.421, year: 2021
Method of publishing: Limited access
https://www-embopress-org.d360prx.biomed.cas.cz/doi/epdf/10.15252/embr.202050785

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.
Permanent Link: http://hdl.handle.net/11104/0321209