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APC anti-mouse CD4 antibody

RRID:AB_312719

Antibody ID

AB_312719

Target Antigen

CD4 See NCBI gene mouse

Proper Citation

(BioLegend Cat# 100516, RRID:AB_312719)

Clonality

monoclonal antibody

Comments

Applications: FC

Clone ID

Clone RM4-5

Host Organism

rat

LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade.

  • Sheng W
  • Cell
  • 2018 Jun 18

Literature context:


Abstract:

Chromatin regulators play a broad role in regulating gene expression and, when gone awry, can lead to cancer. Here, we demonstrate that ablation of the histone demethylase LSD1 in cancer cells increases repetitive element expression, including endogenous retroviral elements (ERVs), and decreases expression of RNA-induced silencing complex (RISC) components. Significantly, this leads to double-stranded RNA (dsRNA) stress and activation of type 1 interferon, which stimulates anti-tumor T cell immunity and restrains tumor growth. Furthermore, LSD1 depletion enhances tumor immunogenicity and T cell infiltration in poorly immunogenic tumors and elicits significant responses of checkpoint blockade-refractory mouse melanoma to anti-PD-1 therapy. Consistently, TCGA data analysis shows an inverse correlation between LSD1 expression and CD8+ T cell infiltration in various human cancers. Our study identifies LSD1 as a potent inhibitor of anti-tumor immunity and responsiveness to immunotherapy and suggests LSD1 inhibition combined with PD-(L)1 blockade as a novel cancer treatment strategy.

Funding information:
  • Intramural NIH HHS - U01-CA84967(United States)
  • NCI NIH HHS - R01 CA118487()
  • NCI NIH HHS - R35 CA210104()
  • NCI NIH HHS - T32 CA207021()

CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells.

  • Yuan X
  • Elife
  • 2017 Nov 24

Literature context:


Abstract:

How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance.

Funding information:
  • NIGMS NIH HHS - T32 GM07270(United States)

Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob.

  • Denzin LK
  • Immunity
  • 2017 Aug 15

Literature context:


Abstract:

Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype. Subsequent bioinformatics and functional analyses of the human H2-Ob homolog, HLA-DOB, revealed both loss- and gain-of-function alleles, which could affect the ability of their carriers to control infections with human hepatitis B (HBV) and C (HCV) viruses. Thus, understanding of the previously unappreciated role of H2-O (HLA-DO) in immunity to infections may suggest new approaches in achieving neutralizing immunity to viruses.

Funding information:
  • NCATS NIH HHS - UL1 TR000430()
  • NCI NIH HHS - P30 CA014599()
  • NCI NIH HHS - R01 CA134667()
  • NIAID NIH HHS - R01 AI061484()
  • NIAID NIH HHS - R01 AI117535()
  • NIAID NIH HHS - T32 AI007090()

Analyses of a Mutant Foxp3 Allele Reveal BATF as a Critical Transcription Factor in the Differentiation and Accumulation of Tissue Regulatory T Cells.

  • Hayatsu N
  • Immunity
  • 2017 Aug 15

Literature context:


Abstract:

Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. Mechanistically, repressed BATF expression contributed to these A384T effects. At the molecular level, the A384T mutation altered Foxp3 interactions with its specific target genes including Batf by broadening its DNA-binding specificity. Our findings identify BATF as a critical regulator of tissue Treg cells and suggest that sequence-specific perturbations of Foxp3-DNA interactions can influence specific facets of Treg cell physiology and the immunopathologies they regulate.