European Journal of Immunology · 2021 · 12 citations · 36 references
Life SciencesImmunologyMolecular BiologyImmunoregulationInflammationMucosal ImmunologyB Cell BiologyB Cell RegulationChemokine SignalingImmune Cell TraffickingLeukocyte TraffickingLymphocyte TraffickingB Cell TraffickingEgress From Lymphoid OrgansInflammation-driven TraffickingIntestinal Mucosal ImmunityLymphocyte EgressLymphocyte MigrationLymphocyte PhysiologyTrafficking In Lymphoid Organs
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.
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