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Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response.
Sigrid Bülow1, Katharina U Ederer1, Jonas M Holzinger1
1Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.
Cell Reports
|March 8, 2024
Summary
Bactericidal/permeability-increasing protein (BPI) activates dendritic cells (DCs), promoting T helper 22 (Th22) cell differentiation. This BPI-DC-Th22 axis is crucial for maintaining intestinal homeostasis and protecting against colitis.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Neutrophil-derived bactericidal/permeability-increasing protein (BPI) exhibits known antimicrobial functions.
- The role of BPI in modulating adaptive immune responses remains largely unexplored.
Purpose of the Study:
- To investigate the function of BPI in dendritic cell (DC) activation and subsequent T cell differentiation.
- To determine the role of the BPI-DC-Th22 axis in intestinal inflammation and homeostasis.
Main Methods:
- Bone marrow-derived dendritic cells (BMDCs) were cultured and stimulated with BPI.
- Cytokine production in response to BPI was analyzed using ELISA and flow cytometry.
- T helper 22 (Th22) cell differentiation was assessed.
- Dextran sodium sulfate (DSS)-induced colitis models in BPI-deficient and wild-type mice were employed.
Main Results:
- BPI potently activates murine BMDCs, inducing the secretion of IL-2, IL-6, and TNF-α.
- BPI stimulation of BMDCs promotes the differentiation of naive CD4+ T cells into Th22 cells, characterized by IL-22 production.
- BPI-deficient mice exhibit exacerbated disease severity in DSS-induced colitis, correlating with impaired IL-22 induction.
- Intestinal microbiota influences BPI-dependent IL-22 induction in CD4+ T cells from mesenteric lymph nodes.
Conclusions:
- BPI serves as a potent activator of DCs, driving Th22 cell differentiation.
- The BPI-mediated DC-Th22 cell pathway plays a significant role in maintaining intestinal homeostasis.
- BPI is a key mediator in the immune response to gut microbiota and in protection against inflammatory conditions like colitis.
Keywords:
CP: ImmunologyDAMPT cellsTh22alarminbactericidal/permeability-increasing proteincolitisdendritic cellsinterleukin-2interleukin-22microbiotaMore Related Videos
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