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SHR Neuro Cancer Cardio Lipid Metab Microb
Kögl, T; Chang, HF; Staniek, J; Chiang, SCC; Thoulass, G; Lao, J; Weißert, K; Dettmer-Monaco, V; Geiger, K; Manna, PT; Beziat, V; Momenilandi, M; Tu, SM; Keppler, SJ; Pattu, V; Wolf, P; Kupferschmid, L; Tholen, S; Covill, LE; Ebert, K; Straub, T; Groß, M; Gather, R; Engel, H; Salzer, U; Schell, C; Maier, S; Lehmberg, K; Cornu, TI; Pircher, H; Shahrooei, M; Parvaneh, N; Elling, R; Rizzi, M; Bryceson, YT; Ehl, S; Aichele, P; Ammann, S.
Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.
J Exp Med. 2024; 221(7): e20221122
Doi: 10.1084/jem.20221122
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- Co-authors Med Uni Graz
- Geiger Kerstin
- Keppler Selina Jessica
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Qa-SNARE Proteins - metabolism, genetics
- B-Lymphocytes - immunology, metabolism
- Mice - administration & dosage
- Humans - administration & dosage
- CD4-Positive T-Lymphocytes - immunology, metabolism
- Lymphohistiocytosis, Hemophagocytic - immunology, genetics, metabolism
- Mice, Knockout - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Female - administration & dosage
- Male - administration & dosage
- Germinal Center - immunology, metabolism
- Immunity, Humoral - administration & dosage
- Exocytosis - administration & dosage