Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect

Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect Publisher Pubmed

Kogl T^{1, 2} ; Chang HF³ ; Staniek J^{4, 5} ; Chiang SCC^{6, 7} ; Thoulass G^{2, 4, 8} ; Lao J^{2, 4, 8} ; Weiert K^{2, 4} ; Dettmermonaco V^{4, 9} ; Geiger K^{4, 8, 9} ; Manna PT¹⁰ ; Beziat V^{11, 12, 13} ; Momenilandi M^{11, 12} ; Tu SM³ ; Keppler SJ¹⁴ Show All Authors

Kogl T^{1, 2}
Chang HF³
Staniek J^{4, 5}
Chiang SCC^{6, 7}
Thoulass G^{2, 4, 8}
Lao J^{2, 4, 8}
Weiert K^{2, 4}
Dettmermonaco V^{4, 9}
Geiger K^{4, 8, 9}
Manna PT¹⁰
Beziat V^{11, 12, 13}
Momenilandi M^{11, 12}
Tu SM³
Keppler SJ¹⁴
Pattu V³
Wolf P¹⁵
Kupferschmid L¹⁶
Tholen S¹⁷
Covill LE⁷
Ebert K¹
Straub T¹
Gro M^{2, 4}
Gather R^{2, 4}
Engel H¹
Salzer U^{4, 5}
Schell C¹⁷
Maier S¹⁸
Lehmberg K¹⁸
Cornu TI^{4, 9}
Pircher H¹
Shahrooei M^{19, 20}
Parvaneh N^{21, 22}
Elling R^{4, 23}
Rizzi M^{4, 5, 24, 25, 26}
Bryceson YT^{7, 27, 28}
Ehl S^{2, 4}
Aichele P^{2, 4}
Ammann S^{2, 4}

Show Affiliations

1. Institute for Immunology, Center for Microbiology and Hygiene, Medical Center-University of Freiburg, Freiburg, Germany
2. Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
3. Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany
4. Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany
5. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center- University of Freiburg, Freiburg, Germany
6. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States
7. Department of Medicine, Center for Hematology and Regenerative Medicine Huddinge, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
8. Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany
9. Faculty of Medicine, Institute for Transfusion Medicine and Gene Therapy-University of Freiburg, Freiburg, Germany
10. Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
11. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France
12. Imagine Institute, University of Paris-Cite, Paris, France
13. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
14. Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria
15. Department of Urology, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
16. Institute of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany
17. Department of Pathology, Institute of Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany
18. Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
19. Department of Microbiology, Immunology, Transplantation, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium
20. Dr. Shahrooei Laboratory, Tehran University of Medical Sciences, Tehran, Iran
21. Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
22. Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran
23. Faculty for Medicine, Center for Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Freiburg, Germany
24. Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
25. Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
26. Faculty of Medicine, Clinical Immunology, Medical Center-University of Freiburg, Freiburg, Germany
27. Division of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
28. Broegelmann Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway

Source: The Journal of experimental medicine Published:2024

Abstract

SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity. Detailed analysis of Stx11-deficient mice revealed impaired CD4 T cell help for B cells, associated with disrupted germinal center formation, reduced isotype class switching, and low antibody avidity. Mechanistically, Stx11-/- CD4 T cells exhibit impaired membrane fusion leading to reduced CD107a and CD40L surface mobilization and diminished IL-2 and IL-10 secretion. Our findings highlight a critical role of STX11 in SNARE-mediated membrane trafficking and vesicle exocytosis in CD4 T cells, important for successful CD4 T cell-B cell interactions. Deficiency in STX11 impairs CD4 T cell-dependent B cell differentiation and humoral responses. © 2024 Kogl et al.

Style	Citing Format
MLA	Kogl T, et al.. "Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect." The Journal of experimental medicine, vol. 221, no. 7, 2024, pp. -.
APA	Kogl T, Chang HF, Staniek J, Chiang SCC, Thoulass G, Lao J, Weiert K, Dettmermonaco V, Geiger K, Manna PT, Beziat V, Momenilandi M, Tu SM, Keppler SJ, Pattu V, Wolf P, Kupferschmid L, Tholen S, Covill LE, ... Ammann S (2024). Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect. The Journal of experimental medicine, 221(7), -.
Chicago	Kogl T, Chang HF, Staniek J, Chiang SCC, Thoulass G, Lao J, Weiert K, et al.. "Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect." The Journal of experimental medicine 221, no. 7 (2024): -.
Harvard	Kogl T et al. (2024) 'Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect', The Journal of experimental medicine, 221(7), pp. -.
Vancouver	Kogl T, Chang HF, Staniek J, Chiang SCC, Thoulass G, Lao J, et al.. Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect. The Journal of experimental medicine. 2024;221(7):-.
BibTex	@article{ author = {Kogl T and Chang HF and Staniek J and Chiang SCC and Thoulass G and Lao J and Weiert K and Dettmermonaco V and Geiger K and Manna PT and Beziat V and Momenilandi M and Tu SM and Keppler SJ and Pattu V and Wolf P and Kupferschmid L and Tholen S and Covill LE and Ebert K and Straub T and Gro M and Gather R and Engel H and Salzer U and Schell C and Maier S and Lehmberg K and Cornu TI and Pircher H and Shahrooei M and Parvaneh N and Elling R and Rizzi M and Bryceson YT and Ehl S and Aichele P and Ammann S}, title = {Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect}, journal = {The Journal of experimental medicine}, volume = {221}, number = {7}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Kogl T AU - Chang HF AU - Staniek J AU - Chiang SCC AU - Thoulass G AU - Lao J AU - Weiert K AU - Dettmermonaco V AU - Geiger K AU - Manna PT AU - Beziat V AU - Momenilandi M AU - Tu SM AU - Keppler SJ AU - Pattu V AU - Wolf P AU - Kupferschmid L AU - Tholen S AU - Covill LE AU - Ebert K AU - Straub T AU - Gro M AU - Gather R AU - Engel H AU - Salzer U AU - Schell C AU - Maier S AU - Lehmberg K AU - Cornu TI AU - Pircher H AU - Shahrooei M AU - Parvaneh N AU - Elling R AU - Rizzi M AU - Bryceson YT AU - Ehl S AU - Aichele P AU - Ammann S TI - Patients and Mice With Deficiency in the Snare Protein Syntaxin-11 Have a Secondary B Cell Defect JO - The Journal of experimental medicine VL - 221 IS - 7 SP - EP - PY - 2024 ER -

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