Bardet–Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance
Open accessPublished version of a preprint
Abstract
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.
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The primary cilium can regulate immune responses.
“These reports suggest that the primary cilium can regulate immune responses, although the role of the primary cilium in neuroinflammation remains largely unexplored.”
From Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte (2024) · cites this paper as Tsyklauri et al. 2021
The Abstract reports a connection between Bardet–Biedl syndrome, a ciliopathy, and dysregulated immune systems; the Discussion describes BBSome-dependent changes in B-cell development. But the Discussion says the role of ciliary signaling in these effects needs further study, so the paper does not establish that the primary cilium itself regulates immune responses. (LLM, conf=0.85)
Experimental — accuracy not yet measuredRecent evidence suggests a link between primary cilium defects and autoimmune and allergic diseases.
“Furthermore, recent evidence suggests a link between primary cilium defects and autoimmune and allergic diseases (Tsyklauri et al. 2021; Rizaldy et al. 2021; Toriyama et al. 2023; Toriyama and Ishii 2021).”
From Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte (2024) · cites this paper as Tsyklauri et al. 2021
The Abstract and the section “Autoimmune diseases are more prevalent in BBS patients” link Bardet–Biedl syndrome, a disorder of primary cilia, to increased prevalence of certain autoimmune diseases. The passages do not establish a link to allergic diseases; a search for allergy and related terms found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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Cites
Global epidemiology of hyperthyroidism and hypothyroidism
Taylor, P. N., Albrecht, D., Scholz, A., Gutierrez-Buey, G., Lazarus, J. H., Dayan, C. M., & Okosieme, O. E. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.18 · Cited by 1,552 · see citing works
Pro-inflammatory cytokines: The link between obesity and osteoarthritis
Wang, T., & He, C. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.10.002 · Cited by 1,034 · see citing works
Berbari, N. F., Lewis, J. S., Bishop, G. A., Askwith, C. C., & Mykytyn, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711027105 · Cited by 474 · see citing works
The impact of obesity on the immune response to infection
Milner, J. J., & Beck, M. A. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000158 · Cited by 439 · see citing works
Expression of primary cilia in mammalian cells
WHEATLEY, D. N., WANG, A. M., & STRUGNELL, G. E. (1996) · Cell Biology International · doi:10.1006/cbir.1996.0011 · Cited by 378 · see citing works
BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone
Ye, F., Nager, A. R., & Nachury, M. V. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709041 · Cited by 256 · see citing works
Khaodhiar, L., Ling, P., Blackburn, G. L., & Bistrian, B. R. (2004) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607104028006410 · Cited by 243 · see citing works
Inactivation of Bardet-Biedl syndrome genes causes kidney defects
Guo, D.-F., Beyer, A. M., Yang, B., Nishimura, D. Y., Sheffield, V. C., & Rahmouni, K. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00150.2010 · Cited by 27 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Halac U, Herzog D (2012) Bardet-Biedl Syndrome, Crohn Disease, primary sclerosing cholangitis, and autoantibody positive thyroiditis: a case report and a review of a cohort of BBS patients. Case Rep Med 2012: 209827
- Ohno T, Aune D, Heath AK (2020) Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies. Sci Rep 10: 16006
- Song RH, Wang B, Yao QM, Li Q, Jia X, Zhang JA (2019) The impact of obesity on thyroid autoimmunity and dysfunction: a systematic review and meta- analysis. Front Immunol 10: 2349
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Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte
Muhamad, N. A., Masutani, K., Furukawa, S., Yuri, S., Toriyama, M., Matsumoto, C., Itoh, S., Shinagawa, Y., Isotani, A., Toriyama, M., et al. (2024) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-024-01482-5 · Cited by 8 · see citing works
- Authors
- Tsyklauri, O., Niederlova, V., Forsythe, E., Prasai, A., Drobek, A., Kasparek, P., Sparks, K., Trachtulec, Z., Prochazka, J., Sedlacek, R., Beales, P., Huranova, M., & Stepanek, O.
- Affiliations
- Czech Academy of Sciences (CZ)
- Great Ormond Street Hospital (GB)
- ORCID
- Venue
- The EMBO Reports
- Published
- 2021-01-11
- Volume
- 22
- Issue
- 2
- Pages
- e50785-e50785
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC7857422
- OpenAlex
- W3120402574
- Cited by
- 39
- References
- 8
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 5 · 2021: 4 · 2020: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- EMBO Reports (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London
- Grantová Agentura České Republiky (17-20613Y)
- Grantová Agentura, Univerzita Karlova (1706119)
- European Molecular Biology Organization (3259)
- Akademie Věd České Republiky (RVO 68378050)
- Czech Academy of Sciences, Purkyne Fellowship
- Charles University, Faculty of Science
- Ministerstvo Školství, Mládeže a Tělovýchovy (LM2015040, LM2018126, OP RDI CZ.1.05/2.1.00/19.0395, OP RDI BIOCEV CZ.1.05/1.1.00/02.0109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- Bardet-Biedl syndrome, ciliopathies, primary cilia, hematopoiesis, autoimmune disease, BBSome, BBS4, B cell development, Wnt signaling, CXCL12, mesenchymal stem cells, obesity, erythrocytes, platelets, self-tolerance
- MeSH terms
- Animals, Autoimmune Diseases, Cilia, Disease Models, Animal, Hematopoiesis, Humans, Microtubule-Associated Proteins, Mutation, Bardet-Biedl Syndrome, Mice
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