CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid

Asano, Kenichi; Kikuchi, Kenta; Tanaka, Masato

doi:10.1093/jb/mvy050

Cited by 31 publications

(30 citation statements)

References 69 publications

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“…3d) cells localized more distally, closer to the tips of the villi where exposure to apoptotic epithelial cells, and intestinal bacteria and their products would be more prominent. In contrast, the majority of CD169 + cells are concentrated closer to the crypt base, as well as within the submucosa 14,38 (Fig. 3b).…”

Section: Commensal Microbiota Globally Affects the Development And Gementioning

confidence: 98%

“…We next determined the ability of these two colon MP subpopulations to capture systemic antigens, since prior studies had identified CD169 + MPs in the spleen and LNs as "gatekeepers" at the blood-LN interface. 38,39 F4/80 + cells closely associated with blood vessels avidly took up systemically administered 10kD dextran (Dex) ( Fig. 3c), which was further localized to the CD11c − CD169 + CD206 hi cell population ( Fig.…”

Section: Commensal Microbiota Globally Affects the Development And Gementioning

confidence: 99%

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Commensal microbiota drive the functional diversification of colon macrophages

et al. 2020

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Mononuclear phagocytes are a heterogeneous population of leukocytes essential for immune homeostasis that develop tissuespecific functions due to unique transcriptional programs driven by local microenvironmental cues. Single cell RNA sequencing (scRNA-seq) of colonic myeloid cells from specific pathogen free (SPF) and germ-free (GF) C57BL/6 mice revealed extensive heterogeneity of both colon macrophages (MPs) and dendritic cells (DCs). Modeling of developmental pathways combined with inference of gene regulatory networks indicate two major trajectories from common CCR2 + precursors resulting in colon MP populations with unique transcription factors and downstream target genes. Compared to SPF mice, GF mice had decreased numbers of total colon MPs, as well as selective proportional decreases of two major CD11c + CD206 int CD121b + and CD11c − CD206 hi CD121b − colon MP populations, whereas DC numbers and proportions were not different. Importantly, these two major colon MP populations were clearly distinct from other colon MP populations regarding their gene expression profile, localization within the lamina propria (LP) and ability to phagocytose macromolecules from the blood. These data uncover the diversity of intestinal myeloid cell populations at the molecular level and highlight the importance of microbiota on the unique developmental as well as anatomical and functional fates of colon MPs.

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Section: Commensal Microbiota Globally Affects the Development And Gementioning

confidence: 98%

Section: Commensal Microbiota Globally Affects the Development And Gementioning

confidence: 99%

Commensal microbiota drive the functional diversification of colon macrophages

et al. 2020

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“…We have previously described an alternative in vivo targeting strategy for the activation of CD8 + T cell responses in mice [30,31]. High expression of CD169, also known as sialoadhesin and Siglec-1, identifies a unique subset of macrophages in the marginal zone of the spleen and the subcapsular sinus in the lymph node with a privileged location for uptake of Ags (reviewed by [32,33,34,35]). In previous studies, we have shown that ovalbumin (OVA) targeted to CD169 induces T cell responses that rely on Batf3-dependent cDC1s [30,36].…”

Section: Introductionmentioning

confidence: 99%

Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans

Dinther

Venegas

Veninga

et al. 2019

Cancers

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The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169+ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans.

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“…MyD88 is involved in innate immune signaling in both macrophages and DCs in response to sHZ, therefore we speculate that both cell types may have the ability to compensate each other for the loss of MyD88 in either cell type. Moreover CD169 + macrophages in the LN subcapsular sinus could efficiently capture particulate materials for cross‐presentation and elicit innate signals . However, since CD169 + macrophages are resistant to gene deletion using LysM cre transgenic line , it remains a limitation to address whether MyD88 in CD169 + macrophages is crucial for sHZ's adjuvanticity.…”

Section: Resultsmentioning

confidence: 99%

B cell‐intrinsic MyD88 signaling controls IFN‐γ‐mediated early IgG2c class switching in mice in response to a particulate adjuvant

et al. 2019

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Adjuvants improve the potency of vaccines, but the modes of action (MOAs) of most adjuvants are largely unknown. TLR-dependent and -independent innate immune signaling through the adaptor molecule MyD88 has been shown to be pivotal to the effects of most adjuvants; however, MyD88's involvement in the TLR-independent MOAs of adjuvants is poorly understood. Here, using the T-dependent antigen NIPOVA and a unique particulate adjuvant called synthetic hemozoin (sHZ), we show that MyD88 is required for early GC formation and enhanced antibody class-switch recombination (CSR) in mice. Using cell-type-specific MyD88 KO mice, we found that IgG2c class switching, but not IgG1 class switching, was controlled by B cell-intrinsic MyD88 signaling. Notably, IFN-γ produced by various cells including T cells, NK cells, and dendritic cells was the primary cytokine for IgG2c CSR and B-cell intrinsic MyD88 is required for IFN-γ production. Moreover, IFN-γ receptor (IFNγR) deficiency abolished sHZ-induced IgG2c production, while recombinant IFN-γ administration successfully rescued IgG2c CSR impairment in mice lacking B-cell intrinsic MyD88. Together, our results show that B cell-intrinsic MyD88 signaling is involved in the MOA of certain particulate adjuvants and this may enhance our specific understanding of how adjuvants and vaccines work.Keywords: adjuvant r B cells r class switching r IFN-γ r intrinsic MyD88Additional supporting information may be found online in the Supporting Information section at the end of the article.

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CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid

Cited by 31 publications

References 69 publications

Commensal microbiota drive the functional diversification of colon macrophages

Commensal microbiota drive the functional diversification of colon macrophages

Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans

B cell‐intrinsic MyD88 signaling controls IFN‐γ‐mediated early IgG2c class switching in mice in response to a particulate adjuvant

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