InVivoMAb anti-mouse IL-1 R (CD121a)

CloneCatalog #Category
JAMA-147 BE0256InVivoMAb Antibodies
$150 - $3920 Login for Academic & Non-profit Pricing

About InVivoMAb anti-mouse IL-1 R (CD121a)

The JAMA-147 monoclonal antibody reacts with mouse IL-1 receptor (IL-1 R) type 1 also known as CD121a. IL-1 R is an 80 kDa transmembrane glycoprotein and a member of the immunoglobulin superfamily. The receptor is expressed on T cells, thymocytes, dendritic cells, fibroblasts, vascular endothelial cells, epithelial cells and neural cells. IL-1 R type 1 can bind both IL-1α and IL-1β. Upon ligand binding the type I receptor mediates all the known IL-1 biological responses.

InVivoMAb anti-mouse IL-1 R (CD121a) Specifications

Isotype Armenian Hamster IgG, κ
Immunogen Extracellular domain of mouse IL-1 R type 1
Reported Applications

in vivo IL-1 R blockade

in vitro IL-1 R blockade

  • PBS, pH 6.0 0.01% Tween

  • Contains no stabilizers or preservatives
  • <2EU/mg (<0.002EU/μg)
  • Determined by LAL gel clotting assay
  • >95%
  • Determined by SDS-PAGE
Sterility 0.2 μM filtered
Production Purified from tissue culture supernatant in an animal free facility
Purification Protein G
RRID AB_2661843
Molecular Weight 150 kDa
Storage The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.

Application References

InVivoMAb anti-mouse IL-1 R (CD121a)

  • in vivo IL-1 R blockade

Singh, S., et al. (2021). "IL-1alpha Mediates Innate and Acquired Resistance to Immunotherapy in Melanoma." J Immunol 206(8): 1966-1975. PubMed

Inflammation has long been associated with cancer initiation and progression; however, how inflammation causes immune suppression in the tumor microenvironment and resistance to immunotherapy is not well understood. In this study, we show that both innate proinflammatory cytokine IL-1alpha and immunotherapy-induced IL-1alpha make melanoma resistant to immunotherapy. In a mouse melanoma model, we found that tumor size was inversely correlated with response to immunotherapy. Large tumors had higher levels of IL-1alpha, Th2 cytokines, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and regulatory T cells but lower levels of IL-12, Th1 cytokines, and activated T cells. We found that therapy with adenovirus-encoded CD40L (rAd.CD40L) increased tumor levels of IL-1alpha and PMN-MDSCs. Blocking the IL-1 signaling pathway significantly decreased rAd.CD40L-induced PMN-MDSCs and their associated PD-L1 expression in the tumor microenvironment and enhanced tumor-specific immunity. Similarly, blocking the IL-1 signaling pathway improved the antimelanoma activity of anti-PD-L1 Ab therapy. Our study suggests that blocking the IL-1alpha signaling pathway may increase the efficacy of immunotherapies against melanoma.

  • in vivo IL-1 R blockade

Kongsomboonvech, A. K., et al. (2020). "Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5." PLoS Pathog 16(8): e1008327. PubMed

Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are not fully elucidated, we investigated requirements for eliciting naïve CD8 T cell IFNγ responses to a vacuolar resident antigen of T. gondii, TGD057. Naïve TGD057 antigen-specific CD8 T cells (T57) were isolated from transnuclear mice and responded to parasite-infected bone marrow-derived macrophages (BMDMs) in an antigen-dependent manner, first by producing IL-2 and then IFNγ. T57 IFNγ responses to TGD057 were independent of the parasite’s protein export machinery ASP5 and MYR1. Instead, host immunity pathways downstream of the regulatory Immunity-Related GTPases (IRG), including partial dependence on Guanylate-Binding Proteins, are required. Multiple T. gondii ROP5 isoforms and allele types, including ‘avirulent’ ROP5A from clade A and D parasite strains, were able to suppress CD8 T cell IFNγ responses to parasite-infected BMDMs. Phenotypic variance between clades B, C, D, F, and A strains suggest T57 IFNγ differentiation occurs independently of parasite virulence or any known IRG-ROP5 interaction. Consistent with this, removal of ROP5 is not enough to elicit maximal CD8 T cell IFNγ production to parasite-infected cells. Instead, macrophage expression of the pathogen sensors, NLRP3 and to a large extent NLRP1, were absolute requirements. Other members of the conventional inflammasome cascade are only partially required, as revealed by decreased but not abrogated T57 IFNγ responses to parasite-infected ASC, caspase-1/11, and gasdermin D deficient cells. Moreover, IFNγ production was only partially reduced in the absence of IL-12, IL-18 or IL-1R signaling. In summary, T. gondii effectors and host machinery that modulate parasitophorous vacuolar membranes, as well as NLR-dependent but inflammasome-independent pathways, determine the full commitment of CD8 T cells IFNγ responses to a vacuolar antigen.

  • in vivo IL-1 R blockade

Allen, B. M., et al. (2020). "Systemic dysfunction and plasticity of the immune macroenvironment in cancer models." Nat Med 26(7): 1125-1134. PubMed

Understanding of the factors governing immune responses in cancer remains incomplete, limiting patient benefit. In this study, we used mass cytometry to define the systemic immune landscape in response to tumor development across five tissues in eight mouse tumor models. Systemic immunity was dramatically altered across models and time, with consistent findings in the peripheral blood of patients with breast cancer. Changes in peripheral tissues differed from those in the tumor microenvironment. Mice with tumor-experienced immune systems mounted dampened responses to orthogonal challenges, including reduced T cell activation during viral or bacterial infection. Antigen-presenting cells (APCs) mounted weaker responses in this context, whereas promoting APC activation rescued T cell activity. Systemic immune changes were reversed with surgical tumor resection, and many were prevented by interleukin-1 or granulocyte colony-stimulating factor blockade, revealing remarkable plasticity in the systemic immune state. These results demonstrate that tumor development dynamically reshapes the composition and function of the immune macroenvironment.

  • in vivo IL-1 R blockade

Choi, G. E., et al. (2018). "Autophagy deficiency in myeloid cells exacerbates eosinophilic inflammation in chronic rhinosinusitis." J Allergy Clin Immunol 141(3): 938-950 e912. PubMed

BACKGROUND: Eosinophilic inflammation is a major pathologic feature of chronic rhinosinusitis (CRS) and is frequently associated with severe refractory disease. Prostaglandin (PG) D2 levels are increased in patients with CRS, and PGD2 is an important contributing factor to eosinophilic inflammation. Autophagy has a pleiotropic effect on immune responses and disease pathogenesis. Recent studies suggest the potential involvement of autophagy in patients with CRS and the PG pathway. OBJECTIVE: We sought to investigate whether altered function of autophagy is associated with eosinophilic inflammation and dysregulated production of PGD2 in patients with CRS. METHODS: We used myeloid cell-specific deletion of autophagy-related gene 7 (Atg7), which is vital for autophagy, and investigated the effects of impaired autophagy on eosinophilic inflammation in a murine model of eosinophilic chronic rhinosinusitis (ECRS). The effect of autophagy on PGD2 production and gene expression profiles associated with allergy and the PG pathway were assessed. RESULTS: We found that impaired autophagy in myeloid cells aggravated eosinophilia, epithelial hyperplasia, and mucosal thickening in mice with ECRS. This aggravation was associated with gene expression profiles that favor eosinophilic inflammation, TH2 response, mast cell infiltration, and PGD2 dysregulation. Supporting this, PGD2 production was also increased significantly by impaired autophagy. Among other myeloid cells, macrophages were associated with autophagy deficiency, leading to increased IL-1beta levels. Macrophage depletion or blockade of IL-1 receptor led to alleviation of eosinophilic inflammation and sinonasal anatomic abnormalities associated with autophagy deficiency. CONCLUSION: Our results suggest that impaired autophagy in myeloid cells, particularly macrophages, has a causal role in eosinophilic inflammation and ECRS pathogenesis.

    Gimblet, C., et al. (2017). "Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation." Cell Host Microbe 22(1): 13-24.e14. PubMed

    Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases.

    • in vivo IL-1 R blockade

    Naik, S., et al. (2017). "Inflammatory memory sensitizes skin epithelial stem cells to tissue damage." Nature 550(7677): 475-480. PubMed

    The skin barrier is the body’s first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of the inflammasome. The absence of AIM2 or its downstream effectors, caspase-1 and interleukin-1beta, erases the ability of EpSCs to recollect inflammation. Although EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity probably increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.

    • in vivo IL-1 R blockade

    Lin, C. C., et al. (2016). "IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation." J Exp Med 213(2): 251-271. PubMed

    The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX-IL-1-Bhlhe40 pathway active in EAE.

    • in vitro IL-1 R blockade

    Ha, H. L., et al. (2014). "IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms." Proc Natl Acad Sci U S A 111(33): E3422-3431. PubMed

    Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor CIKS/Act1. Here we identify critical roles of CIKS/Act1-mediated signaling in imiquimod-induced psoriatic inflammation, a mouse model that shares features with the human disease. We found that IL-17 cytokines/CIKS-mediated signaling into keratinocytes is essential for neutrophilic microabscess formation and contributes to hyperproliferation and markedly attenuated differentiation of keratinocytes, at least in part via direct effects. In contrast, IL-17 cytokines/CIKS-mediated signaling into nonkeratinocytes, particularly into dermal fibroblasts, promotes cellular infiltration and, importantly, leads to enhanced the accumulation of IL-17-producing gammadeltaT cells in skin, comprising a positive feed-forward mechanism. Thus, CIKS-mediated signaling is central in the development of both dermal and epidermal hallmarks of psoriasis, inducing distinct pathologies via target cell-specific effects. CIKS-mediated signaling represents a potential therapeutic target in psoriasis.