Wnt5A signaling supports antigen processing and CD8 T cell activation

Sarraf, Tresa Rani; Sen, Malini

doi:10.3389/fimmu.2022.960060

Cited by 4 publications

(3 citation statements)

References 59 publications

(18 reference statements)

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“…BMDMs and OT‐II cell adherence were analyzed by mean fluorescence intensity ratio of T cell (CD4: red) and BMDMs‐derived M2 (CD11b: green). 37 …”

Section: Methodsmentioning

confidence: 99%

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Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

Wu,

Shi,

Liu

et al. 2024

CNS Neurosci Ther

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AimsGlioblastoma is the most frequent and aggressive primary brain tumor, characterized by rapid disease course and poor treatment responsiveness. The abundance of immunosuppressive macrophages in glioblastoma challenges the efficacy of novel immunotherapy.MethodsBulk RNA‐seq and single‐cell RNA‐seq of glioma patients from public databases were comprehensively analyzed to illustrate macrophage infiltration patterns and molecular characteristics of podoplanin (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on macrophage immunosuppressive polarization was investigated using a co‐culture system. Bone marrow‐derived macrophages (BMDMs) and OT‐II T cells isolated from BALB/c and OT‐II mice respectively were co‐cultured to determine T‐cell adherence. Pathway alterations were probed through RNA sequencing and western blot analyses.ResultsOur findings demonstrated that PDPN is notably correlated with the expression of CD68 and CD163 in glioma tissues. Additionally, macrophages phagocytosing PDPN‐containing EVs (EVsPDPN) from GBM cells presented increased CD163 expression and augmented secretion of immunoregulatory cytokine (IL‐6, IL‐10, TNF‐α, and TGF‐β1). PDPN within EVs was also associated with enhanced phagocytic activity and reduced MHC II expression in macrophages, compromising CD4+ T‐cell activation.ConclusionsThis investigation underscores that EVsPDPN derived from glioblastoma cells contributes to M2 macrophage‐mediated immunosuppression and is a potential prognostic marker and therapeutic target in glioblastoma.

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“…BMDMs and OT‐II cell adherence were analyzed by mean fluorescence intensity ratio of T cell (CD4: red) and BMDMs‐derived M2 (CD11b: green). 37 …”

Section: Methodsmentioning

confidence: 99%

“…After fluorescent secondary antibody (Yeasen, China) was incubated for 30 min at room temperature (25°C), images were taken. BMDMs and OT‐II cell adherence were analyzed by mean fluorescence intensity ratio of T cell (CD4: red) and BMDMs‐derived M2 (CD11b: green) 37 …”

Section: Methodsmentioning

confidence: 99%

Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

Wu,

Shi,

Liu

et al. 2024

CNS Neurosci Ther

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“…Pre-exposure to Wnt5a, induced phenotypic changes in monocytes, macrophages and dendritic cells, dependent on Toll-like receptors, mediating the innate immune response [10][11][12]. Additionally, Wnt5a signaling contributed to CD4 T cell homeostasis and activation of CD8 T cell, which triggered the adaptive immunity [13,14]. Increasing evidence suggests that Wnt5a signaling may play a crucial role in the in ammatory diseases [9,10,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

Ji,

Zhou,

Wang

et al. 2023

Preprint

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Background Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. Methods Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemistry staining. Results Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to that in healthy controls and were positively correlated with liver injury markers and the HBV DNA load. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression than those with lower hepatic inflammatory grades. In addition, the cut off value of 12.59 for Wnt5a mRNA level was a strong indicator for identifying ACHBLF from CHB. Conclusions We indicated that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in the exacerbation of chronic HBV infection procedure.

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Therapeutic potential of rWnt5A in curbing Leishmania donovani infection

Maity,

Sengupta,

Sen

2023

Infect Immun

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In view of the antagonism of Wnt5A signaling toward microbial pathogens, we were interested in evaluating the therapeutic potential of recombinant Wnt5A (rWnt5A) in curbing Leishmania donovani infection. Initially, using L. donovani -infected RAW 264.7 and peritoneal macrophages, we demonstrated that application of rWnt5A as opposed to the vehicle control to the infected cells significantly dampens L. donovani infection. Inhibition of infection was associated with increase in cell-associated reactive oxygen species (ROS), and blocked by the ROS production inhibitor diphenylene iodonium chloride (DPI). rWnt5A, but not the vehicle control (PBS: phosphate-buffered saline) administration to L. donovani -infected mice appreciably reduced the infection load, and inhibited disease progression as evident from the preservation of splenic white pulp architecture. rWnt5A administration, moreover, led to elevation of both cell-associated ROS and the activation of splenic T cells. Substantial increase in T cell-associated Interleukin-2 (IL-2) and Granzyme B (GRB) upon exposure of splenic lymphocytes harvested from rWnt5A-treated mice to L. donovani -infected RAW 264.7 macrophages in vitro validated the occurrence of L. donovani -responsive T cell activation in vivo . In summary, this study unveils the therapeutic potential of rWnt5A in curbing L. donovani infection and the progression of experimental visceral leishmaniasis possibly through increase in cellular ROS and T cell activation. Accordingly, it opens up a new avenue of investigation into the use of rWnt5A as a therapeutic agent for restraining the progression of drug-resistant L. donovani infection.

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Wnt5A signaling supports antigen processing and CD8 T cell activation

Cited by 4 publications

References 59 publications

Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

Therapeutic potential of rWnt5A in curbing Leishmania donovani infection

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