HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis. 2021

Lorenzo Spagnuolo, and Viola Puddinu, and Noémie Boss, and Thibaud Spinetti, and Anne Oberson, and Jerome Widmer, and Inès Mottas, and Christian Hotz, and Marco E Bianchi, and Mariagrazia Uguccioni, and Carole Bourquin
Chair of Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.

High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1-CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1-CXCL12 complex in PPs than in other lymphoid organs. HMGB1-CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1-CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010581 Peyer's Patches Lymphoid tissue on the mucosa of the small intestine. Patches, Peyer's,Peyer Patches,Peyers Patches
D002634 Chemotaxis, Leukocyte The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction. Leukotaxis,Leukocyte Chemotaxis
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054377 Chemokine CXCL12 A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing. CXCL12 Chemokine,Stromal Cell-Derived Factor-1beta,Chemokine (C-X-C Motif) Ligand 12,Pre-B-Cell Growth-Stimulating Factor,SDF-1alpha,SDF-1beta,SDF1-3'A,Stromal Cell-Derived Factor 1,Stromal Cell-Derived Factor-1alpha,CXCL12, Chemokine,Cell-Derived Factor-1beta, Stromal,Chemokine, CXCL12,Growth-Stimulating Factor, Pre-B-Cell,Pre B Cell Growth Stimulating Factor,SDF 1alpha,SDF 1beta,SDF1 3'A,Stromal Cell Derived Factor 1,Stromal Cell Derived Factor 1alpha,Stromal Cell Derived Factor 1beta
D018928 Immunity, Mucosal Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body. Immune Response, Mucosal,Mucosal Immunity,Immune Responses, Mucosal,Mucosal Immune Response,Mucosal Immune Responses
D024243 HMGB1 Protein A 24-kDa HMGB protein that binds to and distorts the minor grove of DNA. HMG1,Amphoterin,Box Protein 1, High Mobility Group,FM1 Gene Product,HMG 1 Protein,HMG-1 Protein,HMGB1,Heparin-Binding Protein p30,Heparin Binding Protein p30,p30, Heparin-Binding Protein

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