APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa
| Autor: | Carine Bosshard, Eddy Roosnek, Thomas Matthes, Stéphane Durual, Pascal Schneider, Christophe P. Frossard, Rudolf H. Zubler, Christiane Favre, Olivier Donzé, Bertrand Huard, Samir Myit, Thomas Alexander Mckee, Carlo Chizzolini, Jean-Philippe Guyot |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cell Line
Heparan Sulfate Proteoglycans/metabolism Humans Kidney/cytology Mucous Membrane/immunology Neutrophils/metabolism Plasma Cells/immunology Tumor Necrosis Factor Ligand Superfamily Member 13/genetics Tumor Necrosis Factor Ligand Superfamily Member 13/secretion Neutrophils Plasma Cells Tumor Necrosis Factor Ligand Superfamily Member 13 Plasma cell Kidney medicine ddc:616 Lamina propria Mucous Membrane biology Crypt Epithelium Tumor Necrosis Factor Ligand Superfamily Member 13/genetics/secretion General Medicine Epithelium Cell biology medicine.anatomical_structure Lymphatic system Cell culture Immunology Humoral immunity biology.protein Antibody Heparan Sulfate Proteoglycans Research Article |
| Zdroj: | Journal of Clinical Investigation, Vol. 118, No 8 (2008) pp. 2887-2895 Journal of Clinical Investigation, vol. 118, no. 8, pp. 2887-2895 |
| ISSN: | 0021-9738 |
| Popis: | The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how plasma cell survival there is regulated is not known. Here we report that a proliferation-inducing ligand (APRIL) promoted survival of human upper and lower MALT plasma cells by upregulating expression of the antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of APRIL was consistent with such a prosurvival role in MALT. In upper MALT, tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils recruited from the blood infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained secreted APRIL in the subepithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL, giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT mice. Hence, production of APRIL by inflammation-recruited neutrophils may create plasma cell niches in MALT to sustain a local antibody production. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|