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

SYSNO ASEP	0544158
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance
Author(s)	Tsyklauri, Oksana (UMG-J) Niederlová, Veronika (UMG-J)_ORCID Forsythe, E. (GB) Prasai, Avishek (UMG-J) Drobek, Aleš (UMG-J)_ORCID Kašpárek, Petr (UMG-J) Sparks, K. (GB) Trachtulec, Zdeněk (UMG-J)_{RID, ORCID} Procházka, Jan (UMG-J)_ORCID Sedláček, Radislav (UMG-J)_RID Beales, P.L. (GB) Huranová, Martina (UMG-J)_ORCID Štěpánek, Ondřej (UMG-J)_{RID, ORCID}
Number of authors	13
Article number	e50785
Source Title	Embo Reports - ISSN 1469-221X Roč. 22, č. 2 (2021)
Number of pages	18 s.
Publication form	Online - E
Language	eng - English
Country	GB - United Kingdom
Keywords	Bardet-Biedl Syndrome ; ciliopathy ; cxcl12 ; immunity ; obesity
Subject RIV	EB - Genetics ; Molecular Biology
OECD category	Genetics and heredity (medical genetics to be 3)
R&D Projects	GJ17-20613Y GA ČR - Czech Science Foundation (CSF)
	LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Limited access
Institutional support	UMG-J - RVO:68378050
UT WOS	000606482400001
DOI	10.15252/embr.202050785
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2022
Electronic address	https://www-embopress-org.d360prx.biomed.cas.cz/doi/epdf/10.15252/embr.202050785

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