InVivoMAb anti-mouse Siglec-H

Clone Catalog # Category
440c BE0202 InVivoMab Antibodies
$95 - $3250

About InVivoMAb anti-mouse Siglec-H

The 440c monoclonal antibody recognizes mouse Siglec-H, a member of the CD33-related Siglec family. Siglec-H has been shown to be exclusively expressed on plasmacytoid dendritic cells (pDCs) and type I IFN-producing cells (IPC) in naïve mice. IPCs play a major role in the immune response to viruses. The 440c antibody has been shown to inhibit pDC function.

InVivoMAb anti-mouse Siglec-H Specifications

Isotype

Rat IgG2b

Recommended Isotype Control(s) InVivoMAb rat IgG2b isotype control, anti-keyhole limpet hemocyanin(BE0090)
Recommended InVivoPure Dilution Buffer InVivoPure pH 7.0 Dilution Buffer(IP0070)
Immunogen

Purified bone marrow-derived IPCs

Reported Applications
  • in vivo administration
  • Flow cytometry
Endotoxin
  • <2EU/mg (<0.002EU/μg)
  • Determined by LAL gel clotting assay
Purity
  • >95%
  • Determined by SDS-PAGE
Formulation
  • PBS, pH 7.0
  • Contains no stabilizers or preservatives
Sterility

0.2 μM filtered

Production

Purified from tissue culture supernatant in an animal free facility

Purification

Protein G

Storage

The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.

RRID

AB_10949014

Molecular Weight

150 kDa

Application References

InVivoMAb anti-mouse Siglec-H (Clone: 440c)

  Wu, V., et al. (2015). "Plasmacytoid dendritic cell-derived IFNalpha modulates Th17 differentiation during early Bordetella pertussis infection in mice." Mucosal Immunol. doi: 10.1038/mi.2015.101. PubMed

Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNalpha inhibits a rapid increase in Th17 cells. We found that IFNalpha-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNalpha led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNalpha produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNalpha in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.Mucosal Immunology advance online publication 14 October 2015. doi:10.1038/mi.2015.101.

Puttur, F., et al. (2013). "Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance." PLoS Pathog 9(9): e1003648. PubMed

Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon alpha (IFNalpha), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H(+) pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNalpha levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNalpha production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.

Loschko, J., et al. (2011). "Antigen targeting to plasmacytoid dendritic cells via Siglec-H inhibits Th cell-dependent autoimmunity." J Immunol 187(12): 6346-6356. PubMed

Plasmacytoid dendritic cells (PDCs) have been shown to present Ags and to contribute to peripheral immune tolerance and to Ag-specific adaptive immunity. However, modulation of adaptive immune responses by selective Ag targeting to PDCs with the aim of preventing autoimmunity has not been investigated. In the current study, we demonstrate that in vivo Ag delivery to murine PDCs via the specifically expressed surface molecule sialic acid binding Ig-like lectin H (Siglec-H) inhibits Th cell and Ab responses in the presence of strong immune stimulation in an Ag-specific manner. Correlating with sustained low-level MHC class II-restricted Ag presentation on PDCs, Siglec-H-mediated Ag delivery induced a hyporesponsive state in CD4(+) T cells leading to reduced expansion and Th1/Th17 cell polarization without conversion to Foxp3(+) regulatory T cells or deviation to Th2 or Tr1 cells. Siglec-H-mediated delivery of a T cell epitope derived from the autoantigen myelin oligodendrocyte glycoprotein to PDCs effectively delayed onset and reduced disease severity in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by interfering with the priming phase without promoting the generation or expansion of myelin oligodendrocyte glycoprotein-specific Foxp3(+) regulatory T cells. We conclude that Ag delivery to PDCs can be harnessed to inhibit Ag-specific immune responses and prevent Th cell-dependent autoimmunity.

       

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