Journal article
Metabolic fitness of IgA plasma cells in the gut requires DOCK8
Mucosal immunology, v 17(3), pp 431-449
01 Jun 2024
PMID: 38159726
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Dedicator of cytokinesis 8 (DOCK8) mutations lead to a primary immunodeficiency associated with recurrent gastrointestinal infections and poor antibody responses but, paradoxically, heightened IgE to food antigens, suggesting that DOCK8 is central to immune homeostasis in the gut. Using Dock8-deficient mice, we found that DOCK8 was necessary for mucosal IgA production to multiple T cell-dependent antigens, including peanut and cholera toxin. Yet DOCK8 was not necessary in T cells for this phenotype. Instead, B cell-intrinsic DOCK8 was required for maintenance of antigen-specific IgA-secreting plasma cells (PCs) in the gut lamina propria. Unexpectedly, DOCK8 was not required for early B cell activation, migration, or IgA class switching. An unbiased interactome screen revealed novel protein partners involved in metabolism and apoptosis. Dock8-deficient IgA
B cells had impaired cellular respiration and failed to engage glycolysis appropriately. These results demonstrate that maintenance of the IgA
PC compartment requires DOCK8 and suggest that gut IgA
PCs have unique metabolic requirements for long-term survival in the lamina propria.
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Details
- Title
- Metabolic fitness of IgA plasma cells in the gut requires DOCK8
- Creators
- Biyan Zhang - Singapore Immunology NetworkShuting Chen - Yale UniversityXiangyun Yin - Yale UniversityCaleb D. McBride - Northwestern UniversityJake A. Gertie - Yale UniversityMarina Yurieva - Jackson LaboratoryAgata A. Bielecka - Helmholtz Centre for Infection ResearchBrian Hoffmann - Jackson LaboratoryJ. Travis Hinson - UConn HealthJessica Grassmann - Jackson LaboratoryLan Xu - Yale UniversityEmily R. Siniscalco - Yale UniversityArielle Soldatenko - Yale UniversityLaura Hoyt - Yale UniversityJulie Joseph - Drexel UniversityElizabeth B. Norton - Tulane UniversityGowthaman Uthaman - University of Massachusetts Chan Medical SchoolNoah W. Palm - Yale UniversityElise Liu - Yale UniversityStephanie C. Eisenbarth - Northwestern UniversityAdam Williams - Northwestern University
- Publication Details
- Mucosal immunology, v 17(3), pp 431-449
- Publisher
- Elsevier
- Number of pages
- 19
- Grant note
- 1 S10 OD026816-01 / National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) Ira & Diana Riklis Family Research Award in Food Allergy, Food Allergy Research & Education 1 S10 OD026816-01 / National Institutes of Health (100000002) Food Allergy Research and Education (http://data.elsevier.com/vocabulary/SciValFunders/100006423) National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) R01 AI136942; R56 AI155497 / Food Allergy Science Initiative, Inc. Agency for Science, Technology and Research (http://data.elsevier.com/vocabulary/SciValFunders/501100001348) China Scholarship Council-Yale World Scholars
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001253792700001
- Scopus ID
- 2-s2.0-85183023244
- Other Identifier
- 991022202091104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology