CD1dhiCD5+ B cells differentiate into antibody-secreting cells under the stimulation with calreticulin fragment

Zhang, Tengteng; Xia, Yifeng; Zhang, Lijuan; Bao, Wan-Rong; Cheng, Hong; Gao, Xiao‐Ming

doi:10.1007/s13238-013-3062-5

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…As one of the HSPs, soluble CRT protein exhibits potent immunological functions both in vivo and in vitro , such as activating monocytes/macrophages and expanding CD1d hi CD5 + B10 cells [ 13 – 16 ]. Given that elevated levels of soluble CRT in body fluids (serum and synovial fluid) correlate with autoimmune disease and cancer in humans, immunobiological activities of CRT deserves detailed investigation.…”

Section: Resultsmentioning

confidence: 99%

Soluble Calreticulin Induces Tumor Necrosis Factor-α (TNF-α) and Interleukin (IL)-6 Production by Macrophages through Mitogen-Activated Protein Kinase (MAPK) and NFκB Signaling Pathways

Duo

Gong

et al. 2014

IJMS

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We have recently reported that soluble calreticulin (CRT) accumulates in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus. Moreover, following self-oligomerization, soluble recombinant CRT (rCRT) polypeptides exhibit potent immunostimulatory activities including macrophage activation in vitro and antibody induction in vivo. This study was designed to further investigate the underlying molecular mechanisms for soluble CRT-induced macrophage activation. Treatment of murine macrophages with oligomerized rCRT (OrCRT) led to (i) TNF-α and IL-6 transcription and protein expression without affecting intracellular mRNA stability; and (ii) IκBα degradation, NFκB phosphorylation and sustained MAPK phosphorylation in cells. Inhibition of IKK and JNK in macrophages substantially abrogated production of TNF-α and IL-6 induced by OrCRT, while ERK suppression only reduced IL-6 expression in parallel experiments. In vitro, fucoidan, a scavenger receptor A (SRA)-specific ligand, significantly reduced the uptake of FITC-labeled OrCRT by macrophages and subsequent MAPK and NFκB activation, thereby suggesting SRA as one of the potential cell surface receptors for soluble CRT. Together, these data indicate that soluble CRT in oligomerized form could play a pathogenic role in autoimmune diseases through induction of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by macrophages via MAPK-NFκB signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Soluble Calreticulin Induces Tumor Necrosis Factor-α (TNF-α) and Interleukin (IL)-6 Production by Macrophages through Mitogen-Activated Protein Kinase (MAPK) and NFκB Signaling Pathways

Duo

Gong

et al. 2014

IJMS

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“…HSP70), and high-mobility group I (HMGB1) protein [20]. Recombinant CALR fragment was shown to exhibit potent stimulatory activities against B cells [21, 22]. Recently, we reported that activated B cells are increased in ET patients, and can facilitate platelet production mediated by cytokines, such as interleukin (IL)-1β and IL-6 regardless JAK2 V617F mutational status [23].…”

Section: Introductionmentioning

confidence: 99%

Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and triple-negative essential thrombocythemia

et al. 2017

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Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation, CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count (p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients when compared to healthy adults. JAK2- and CALR-mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET (p=0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.

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“…Neutrophils secrete azurocidin, which has been shown to bind to CALR and induce cytokine production in monocytes ( 124 ). A partial recombinant CALR fragment from mice was found to stimulate human monocytes and B cell cytokine secretion ( 125 ), as well as stimulate B cell differentiation into antibody secreting cells ( 126 ). Interestingly, stimulation of macrophages with recombinant CALR induced expression of TNFα and IL-6.…”

Section: Calreticulin Effects On Immune Cell Responsementioning

confidence: 99%

Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds

Sawaya,

Vecin,

Burgess

et al. 2023

Front. Med.

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Calreticulin is recognized as a multifunctional protein that serves an essential role in diverse biological processes that include wound healing, modification and folding of proteins, regulation of the secretory pathway, cell motility, cellular metabolism, protein synthesis, regulation of gene expression, cell cycle regulation and apoptosis. Although the role of calreticulin as an endoplasmic reticulum-chaperone protein has been well described, several studies have demonstrated calreticulin to be a highly versatile protein with an essential role during wound healing. These features make it an ideal molecule for treating a complex, multifactorial diseases that require fine tuning, such as chronic wounds. Indeed, topical application of recombinant calreticulin to wounds in multiple models of wound healing has demonstrated remarkable pro-healing effects. Among them include enhanced keratinocyte and fibroblast migration and proliferation, induction of extracellular matrix proteins, recruitment of macrophages along with increased granulation tissue formation, all of which are important functions in promoting wound healing that are deregulated in chronic wounds. Given the high degree of diverse functions and pro-healing effects, application of exogenous calreticulin warrants further investigation as a potential novel therapeutic option for chronic wound patients. Here, we review and highlight the significant effects of topical application of calreticulin on enhancing wound healing and its potential as a novel therapeutic option to shift chronic wounds into healing, acute-like wounds.

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CD1dhiCD5+ B cells differentiate into antibody-secreting cells under the stimulation with calreticulin fragment

Cited by 4 publications

References 27 publications

Soluble Calreticulin Induces Tumor Necrosis Factor-α (TNF-α) and Interleukin (IL)-6 Production by Macrophages through Mitogen-Activated Protein Kinase (MAPK) and NFκB Signaling Pathways

Soluble Calreticulin Induces Tumor Necrosis Factor-α (TNF-α) and Interleukin (IL)-6 Production by Macrophages through Mitogen-Activated Protein Kinase (MAPK) and NFκB Signaling Pathways

Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and triple-negative essential thrombocythemia

Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds

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