Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells

Sharapova, Tatiana N.; Романова, Е. А.; Ivanova, Olga K.; Yashin, Denis V.; Sashchenko, Lidia P.

doi:10.3390/ijms22136889

Cited by 23 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, granzyme B was found to be incorporated in tumor cells by explicitly binding to mHSP70, which results in perforin-independent apoptosis of the cells [ 44 ]. Moreover, Sharapova and colleagues recently reported another possibility of NK cell activation while investigating a novel exHSP70 target receptor [ 116 ]. They showed that exHSP70 binds TREM-1 on monocytes, leading to the secretion of TNF-α and INF-γ.…”

Section: Role Of Exhsp70: Regulation Of Immune Responsesmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

Linder

Strandmann

2021

Cancers

View full text Add to dashboard Cite

Extracellular vesicles released by tumor cells (T-EVs) are known to contain danger-associated molecular patterns (DAMPs), which are released in response to cellular stress to alert the immune system to the dangerous cell. Part of this defense mechanism is the heat shock protein 70 (HSP70), and HSP70-positive T-EVs are known to trigger anti-tumor immune responses. Moreover, extracellular HSP70 acts as an immunogen that contributes to the cross-presentation of major histocompatibility complex (MHC) class I molecules. However, the release of DAMPs, including HSP70, may also induce chronic inflammation or suppress immune cell activity, promoting tumor growth. Here, we summarize the current knowledge on soluble, membrane-bound, and EV-associated HSP70 regarding their functions in regulating tumor-associated immune cells in the tumor microenvironment. The molecular mechanisms involved in the translocation of HSP70 to the plasma membrane of tumor cells and its release via exosomes or soluble proteins are summarized. Furthermore, perspectives for immunotherapies aimed to target HSP70 and its receptors for cancer treatment are discussed and presented.

show abstract

Section: Role Of Exhsp70: Regulation Of Immune Responsesmentioning

confidence: 99%

“…The cytokines then stimulate CD4 + T-cells to secrete IL-2, finally activating NK cells. Moreover, CD8 + T-cells are also activated by this mechanism and can kill tumor cells via FasL/Fas interaction [ 116 ]. Interestingly, FasL can trigger the secretion of an HSP70-Tag7 complex in T-cells.…”

Section: Role Of Exhsp70: Regulation Of Immune Responsesmentioning

confidence: 99%

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

Linder

Strandmann

2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Earlier investigated peptides 17.1 and 17.1.A capable of binding specifically to the TNFR1 receptor did not exhibit inhibiting effect (Figure 3). It should be noted that N1 reduced the cytotoxic activity initiated both by the full-length Tag7 and the major heat shock protein Hsp70 which can be also considered as a ligand for TREM-1 [10]. In addition, the peptide binding with sTREM-1 expressed on the cell membrane was investigated.…”

Section: Tag7 Protein N-terminal Peptides Interact With the Receptor Trem-1 And Inhibit The Cytotoxic Activity Of Pbmcsmentioning

confidence: 99%

“…The described ligands of TREM-1 include the high mobility group box 1 protein (HMGBI) nuclear protein and the innate immune protein PGLYRP1 (Tag7) [7][8][9]. Our recent study has demonstrated that Hsp70, the major heat shock protein, can be also considered as another ligand for TREM-1 [10]. In turn, TREM-1 is expressed on monocytes, neutrophils, antigen-presenting cells and NK cells, as well as selective T-and B-lymphocyte populations, epithelial cells and fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors

Sharapova

Романова

Chernov

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.

show abstract

“…In recent decades, TREM-1 ligands have been investigated as a potential tool to regulate inflammation. Recently, the following ligands of TREM-1 receptor have been identified: HMGBP1, PGLYRP1 and Hsp70 [ 14 , 23 , 24 , 25 ]. Some evidence suggests that Hsp70 is a novel ligand for TREM-1 and has an impact upon its activation [ 24 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

N-Terminal Peptide of PGLYRP1/Tag7 Is a Novel Ligand for TREM-1 Receptor

Sharapova

Ivanova

Романова

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

An investigation of innate immunity receptors sheds light on the mechanisms of inflammation and associated immune reactions. One of the key immune regulators is the TREM-1 receptor, which is involved in both inflammation and antitumor immune response. In this article, we have obtained a new ligand for the TREM-1 receptor. The peptide, named N3, is a part of the innate immune protein PGLYRP1/Tag7. It is responsible for activating the TREM-1 signaling pathway. Here, we have demonstrated that the N3 peptide acts like other TREM-1 receptor ligands: its binding results in a mild inflammation response and appearance of cytotoxic lymphocytes. We have shown that cytotoxic populations of lymphocytes in N3 peptide-treated PBMCs are similar to those treated with Tag7 or Hsp70. We also determined the part of the N3 peptide responsible for binding to TREM-1. The resulting peptide (N9) consists of nine amino acids and can be considered as a potential peptide that blocks TREM-1 signaling.

show abstract

Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells

Cited by 23 publications

References 33 publications

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors

N-Terminal Peptide of PGLYRP1/Tag7 Is a Novel Ligand for TREM-1 Receptor

Contact Info

Product

Resources

About