Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis

Apoptosis of CD4(+) T cells and T(H)2 polarization are hallmarks of sepsis-induced immunoparalysis. In this study, we characterized sepsis-induced adaptive immune dysfunction and examined whether improving T-cell effector function can improve outcome to sepsis. We found that septic mice produced less antigen-specific T-cell-dependent IgM and IgG(2a) antibodies than sham-treated mice. As early as 24 hours after sepsis, CD4(+) T cells proliferated poorly to T-cell receptor stimulation, despite normal responses to phorbol myristate acetate and ionomycin, and possessed decreased levels of CD3zeta. Five days following immunization, CD4(+) T cells from septic mice displayed decreased antigen-specific proliferation and production of IL-2 and IFN-gamma but showed no difference in IL-4, IL-5, or IL-10 production. Treatment of mice with anti-GITR agonistic antibody restored CD4(+) T-cell proliferation, increased T(H)1 and T(H)2 cytokine production, partially prevented CD3zeta down-regulation, decreased bacteremia, and increased sepsis survival. Depletion of CD4(+) T cells but not CD25(+) regulatory T cells eliminated the survival benefit of anti-GITR treatment. These results indicate that CD4(+) T-cell dysfunction is a key component of sepsis and that improving T-cell effector function may be protective against sepsis-associated immunoparalysis.     

The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions

In phagocytes, GTPases of the Rac family control crucial antimicrobial functions. The RacGAP ArhGAP15 negatively modulates Rac activity in leukocytes, but its in vivo role in innate immunity remains largely unknown. Here we show that neutrophils and macrophages derived from mice lacking ArhGAP15 presented higher Rac activity but distinct phenotypes. In macrophages, the loss of ArhGAP15 induced increased cellular elongation and membrane protrusions but did not modify chemotactic responses. Conversely, the lack of ArhGAP15 in neutrophils affected critical Rac-dependent antimicrobial functions, specifically causing enhanced chemotactic responses, straighter directional migration, amplified reactive oxygen species production, increased phagocytosis, and improved bacterial killing. In vivo, in a model of severe abdominal sepsis, these effects contributed to increase neutrophil recruitment to the site of infection, thereby limiting bacterial growth, controlling infection spread, reducing systemic inflammation, and ultimately improving survival in ArhGAP15-null mice. Altogether, these results demonstrate the relevance of ArhGAP15 in the selective regulation of multiple neutrophil functions, suggesting that ArhGAP15 targeting might be beneficial in specific pathologic settings like severe sepsis.     

Studies Of The Effects Of Pregnancy Serum On Polymorphonuclear Leukocyte Functions

The phagocytosis of both viable and heat-killed Staphylococcus aureus by normal human neutrophils was diminished in the presence of pregnancy serum. Particle ingestion was reduced significantly (P < 0.0025) after 5 minutes of incubation when leukocytes were in 15% serum obtained during the latter phases of gestation. Control sera from normal adult females or males or from cord blood all functioned normally in support of phagocytosis. Intracellular metabolic events occurring after ingestion, including bacterial killing and nitro-blue tetrazolium reduction, were decreased in proportion to the number of particles ingested. Differential studies involving leukocytes obtained from either pregnant or control subjects, when suspended in either pregnancy or control serum pools, showed the inhibition was due to a humoral and not a cellular factor. Mixing experiments demonstrated that serum obtained during gestation contained a suppressor or neutrophil function rather than a deficiency of a factor required for phagocytosis. The pregnancy serum suppressant affected cells, not the particles ingested, and was found to be non-dialyzable and heat-stable. Hydrocortisone added to control sera to exceed the steroid concentrations found in pregnancy sera did not retard phagocytosis nor diminish bactericidal activity. The data suggest that the active serum component exerts its inhibitory action at the cell surface. Since polymorphonuclear leukocytes are important mediators of inflammation and are implicated in the pathogenesis of tissue destruction, the subsidence of inflammatory diseases during gestation could be related, at least in part, to the inhibitory effects of pregnancy serum on leukocyte functions.     

Immunodepression in sepsis and SIRS assessed by ex vivo cytokine production is not a generalized phenomenon: a review

Sepsis and non-infectious systemic inflammatory response syndrome (SIRS) are paradoxically associated with an exacerbated production of cytokines, as assessed by their presence in biological fluids, and a diminished ability of circulating leukocytes to produce cytokine upon in vitro activation. In this review, we depict that the observed cellular hyporeactivity is not a global phenomenon and that some signalling pathways are unaltered and allow the cells to respond normally to certain stimuli. Furthermore, we illustrate that during sepsis and SIRS, cells derived from tissues are either fully responsive to ex vivo stimuli or even primed, in contrast to cells derived from hematopoietic compartments (blood, spleen, etc.) which are hyporeactive. In addition to cytokine production, nuclear factor-kappa B (NF-kappa B) status within leukocytes can be used as a useful marker of hypo- or hyper-reactivity. We illustrate that the immune-depression reported in sepsis and SIRS patients, often revealed by a diminished capacity of leukocytes to respond to lipopolysaccharide, is not a generalized phenomenon and that SIRS is associated with a compartmentalized responsiveness which involves either anergic or primed cells.     

Differential role of neutrophil Fcγ receptor IIIB (CD16) in phagocytosis,bacterial killing,and responses to immune complexes

Objective

To determine the roles played by the neutrophil Fcγ receptor type II (FcγRII) (CD32) and FcγRIIIb (CD16) in phagocytosis, bacterial killing, and activation by immune complexes (ICs) and to test the hypothesis that inhibition of pathologic effector neutrophil function is possible without compromising host defense.

Methods

Receptor function was probed by enzymic removal of FcγRIIIb from the cell surface and by use of Fab/F(ab‘)₂ fragments of monoclonal antibodies to block receptor‐ligand binding. Cells were challenged with (a) serum‐opsonized Staphylococcus aureus, (b) serum‐ and IgG‐opsonized latex particles, and (c) synthetic soluble and insoluble ICs to mimic bacterial and inflammatory stimuli.

Results

Phosphatidylinositol‐phospholipase C treatment removed >97% of surface FcγRIIIb from neutrophils previously treated with tumor necrosis factor α to mobilize intracellular stores of receptor. This treatment profoundly inhibited activation of primed neutrophils by soluble ICs of the type found in diseased rheumatoid joints, but had no effect on phagocytosis and killing of serum‐opsonized S aureus.

Conclusion

FcγRIIIb plays a major role in the secretion of toxic products in response to ICs, but little or no role in the phagocytosis and killing of serum‐opsonized bacteria. The selective suppression of effector neutrophil function is therefore possible. FcγRIIIb, or its intracellular signaling pathway, is a potential therapeutic target in inflammatory diseases such as rheumatoid arthritis, because disruption of its function should decrease inflammatory tissue damage, but not jeopardize host protection against infection.

     

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno‐regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th‐2 type cytokines interleukin (IL)‐4, IL‐5 and IL‐13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC‐only cultures stimulated with SWA. Substantial levels of IL‐13, IL‐10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil‐induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th‐2 type cytokines. This study shows that eosinophils may down‐modulate schistosome‐specific Th‐2 type cytokine responses in S. mansoni‐infected individuals. The mechanism of this immune modulation remains to be elucidated.     

Reprogramming of circulatory cells in sepsis and SIRS

Immune status is altered in patients with sepsis or non-infectious systemic inflammatory response syndrome (SIRS). Reduced ex-vivo TNF production by endotoxin-activated monocytes has been regularly reported. This observation is reminiscent of the phenomenon of endotoxin tolerance, and the term 'leukocyte reprogramming' well defines this phenomenon. This review will outline that the hyporesponsiveness of circulating leukocytes is not a generalized phenomenon in sepsis and SIRS. Indeed, the nature of the insult (i.e. infectious versus non-infectious SIRS; under anesthesia [surgery] or not [trauma, burn]), the nature of the activator used to trigger leukocytes (i.e. different Toll-like receptor ligands or whole bacteria), the nature of the cell culture (i.e. isolated monocytes versus peripheral blood mononuclear cells versus whole blood assays), and the nature of the analyzed cytokines (e.g. IL-1beta versus IL-1ra; TNF versus IL-10) have a profound influence on the outcome of the response.     

Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis

Objective In malaria and sepsis, apoptotic endothelial damage is preventable in vitro by antioxidants and protease inhibitors. Activated protein C, which has anti‐apoptotic effects, improves survival in sepsis. Therefore, we studied whether activated protein C prevents endothelial cell apoptosis, induced by serum from patients with malaria or sepsis. Methods Endothelial cells were incubated with patient sera (Plasmodium falciparum malaria, Escherichia coli sepsis, Staphylococcus aureus sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Activated protein C was used to reduce endothelial cell apoptosis in vitro. The proportion of apoptotic endothelial cells was determined by TUNEL staining. Results The apoptosis‐inducing effect of patient sera or culture supernatants (P. falciparum, E. coli, S. aureus) on endothelial cells was augmented by neutrophils and reduced by activated protein C in the presence of neutrophils. Pre‐incubating either endothelial cells or neutrophils with activated protein C also reduced the endothelial cell apoptosis rate. The pro‐apoptotic effect of P. falciparum supernatant was reduced by pan‐caspase inhibitor and caspase 8 inhibitor, but not by caspase 9 inhibitor. The pro‐apoptotic effect of E. coli and S. aureus supernatants was also reduced by caspase 9 inhibitor. Conclusions Activated protein C protects vascular endothelial cells from apoptosis triggered by patient sera or culture supernatants in combination with neutrophils. It seems to act both on neutrophils and on endothelial cells. Activated protein C blocks caspase‐8‐dependent apoptosis, which accounts for endothelial damage in sepsis and malaria. Therefore, activated protein C might offer clinical benefit not only in sepsis but also in malaria.     

A multidrug-resistant Pseudomonas aeruginosa isolate from a lethal case of sepsis induces necrosis of human neutrophils

A multidrug-resistant Pseudomonas aeruginosa (r-Pa) was isolated from a lethal case of sepsis in a bone marrow transplant recipient. Genotypic analysis of P. aeruginosa isolates demonstrated that sepsis was secondary to gut colonization. The interactions between r-Pa and patient's neutrophils were studied. The results indicate that: (1) the patient's neutrophil killing activity and nitric oxide production against r-Pa or drug sensitive P. aeruginosa (s-Pa) were profoundly impaired; (2) r-Pa cells, but not s-Pa cells or their filtered culture supernatants, induced necrosis of healthy donor neutrophils. Neutrophil necrosis emerges as a remarkable event in the pathogenesis of P. aeruginosa sepsis.     

Innate immune responses against Cryptosporidium parvum infection

Cryptosporidium parvum infects intestinal epithelial cells and is commonly the parasite species involved in mammalian cryptosporidiosis, a major health problem for humans and neonatal livestock. In mice, immunologically mediated elimination of C. parvum requires CD4⁺ T cells and IFN‐γ. However, innate immune responses also have a significant protective role in both adult and neonatal mice. NK cells and IFN‐γ have been shown to be important components in immunity in T and B cell‐deficient mice, but IFN‐γ‐dependent resistance has also been demonstrated in alymphocytic mice. Epithelial cells may play a vital role in immunity as once infected these cells have increased expression of inflammatory chemokines and cytokines and demonstrate antimicrobial killing mechanisms, including production of NO and antimicrobial peptides. Toll‐like receptors facilitate the establishment of immunity in mice and are involved in the development of inflammatory responses of infected epithelial cells and also dendritic cells.     

Phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear cells from synovial fluid of patients with rheumatoid arthritis

The phagocytosis and intracellular killing by synovial fluid (SF) polymorphonuclear cells (PMN) of 10 patients with rheumatoid arthritis was studied. PMN phagocytosis was assessed by morphologic and microbiologic methods and intracellular killing was measured independently of continuous phagocytosis of Staphylococcus aureus. Phagocytosis of S aureus by SF PMN or peripheral blood (PB) PMN was as effective in the presence of synovial fluid as in the presence of serum. On average, SF PMN ingested S aureus opsonized with synovial fluid and serum more efficiently than patient or donor PB PMN did. Enhanced ingestion of S aureus was associated with increased expression of C3 receptors on the membrane of SF PMN. In the presence of heat-inactivated synovial fluid, the capacity of SF PMN to ingest S aureus was greater than that of patient or donor PB PMN. Under these conditions, phagocytic activity was correlated with Fc receptor expression. SF PMN was found to be as active in killing S aureus as PB PMN from healthy donors.     

Stem and progenitor cell systems in liver development and regeneration

The liver comprises two stem/progenitor cell systems: fetal and adult liver stem/progenitor cells. Fetal hepatic progenitor cells, derived from foregut endoderm, differentiate into mature hepatocytes and cholangiocytes during liver development. Adult hepatic progenitor cells contribute to regeneration after severe and chronic liver injuries. However, the characteristics of these somatic hepatic stem/progenitor cells remain unknown. Culture systems that can be used to analyze these cells were recently established and hepatic stem/progenitor cell‐specific surface markers including delta‐like 1 homolog (DLK), cluster of differentiation (CD) 13, CD133, and LIV2 were identified. Cells purified using antibodies against these markers proliferate for an extended period and differentiate into mature cells both in vitro and in vivo. Methods to force the differentiation of human embryonic stem and induced pluripotent stem (iPS) cells into hepatic progenitor cells have been recently established. We demonstrated that the CD13⁺CD133⁺ fraction of human iPS‐derived cells contained numerous hepatic progenitor‐like cells. These analyses of hepatic stem/progenitor cells derived from somatic tissues and pluripotent stem cells will contribute to the development of new therapies for severe liver diseases.     

Course of disease and survival after onset of decompensation in hepatitis B virus‐related cirrhosis

Background: Data regarding the outcome of hepatitis B virus (HBV)‐related cirrhosis after the onset of decompensation is scanty. Method: From January 1998 to December 2008, a retrospective–prospective inception cohort study involving HBV‐related decompensated cirrhotics was performed. Predictors of death and clinical events after the onset of decompensation were evaluated. Patients with co‐infection with hepatitis C virus and/or human immunodeficiency virus, alcohol consumption to any degree and diabetes diagnosed before the detection of liver disease were excluded. Result and analysis: Two hundred and fifty‐three patients (231 males, 139 e‐negative), including 102 untreated patients, were analysed. The mean (±SD) age was 43.0 (±12.0) years. The mean (±SD) follow‐up period was 47 (±47) months. Decompensation was the first presentation of liver disease in 210 (83%) patients. Ascites (70%) and variceal bleed (28%) were predominant modes of decompensation. Forty‐three (17%) patients died (22 vs 14% in untreated and treated cohort, respectively; P=0.002). Type 2 hepato‐renal syndrome was the commonest cause of death (32%). Survival was independent of e‐antigen status. In the total cohorts, predictors of death were occurrence of sepsis with systemic inflammatory response (SIRS), ascites as the initial mode of decompensation, absence of antiviral therapy and events of high‐grade hepatic encephalopathy [hazards ratios (HR) of 4.4, 3.6, 2.2 and 1.7 respectively]. In the untreated cohort, initial decompensation with ascites and development of sepsis with SIRS were independent predictors of death (HR 8.5 and 2.3 respectively), while 5‐year survival was higher in patients having initial decompensation with variceal bleed vs ascites (29 vs 16%, respectively, P=0.002). Conclusion: Decompensation with ascites and sepsis with SIRS predict reduced survival. Antiviral therapy beyond 6 months improves outcome.     

Role of neutrophil and T cell functions in host defense mechanisms of the elderly]

We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.     

In vivo and in vitro phagocytosis of Leishmania (Leishmania) amazonensis promastigotes by B‐1 cells

Leishmaniasis is caused by Leishmania parasites that infect several cell types. The promastigote stage of Leishmania is internalized by phagocytic cells and transformed into the obligate intracellular amastigote form. B‐1 cells are a subpopulation of B cells that are able to differentiate in vitro and in vivo into mononuclear phagocyte‐like cells with phagocytic properties. B‐1 cells use several receptors for phagocytosis, such as the mannose receptor and third complement receptor. Leishmania binds to the same receptors on macrophages. In this study, we demonstrated that phagocytes derived from B‐1 cells (B‐1 CDP) were able to internalize promastigotes of L. (L.) amazonensis in vitro. The internalized promastigotes differentiated into amastigotes. Our results showed that the phagocytic index was higher in B‐1 CDP compared to peritoneal macrophages and bone marrow‐derived macrophages. The in vivo phagocytic ability of B‐1 cells was also demonstrated. Parasites were detected inside purified B‐1 cells after intraperitoneal infection with L. (L.) amazonensis promastigotes. Intraperitoneal stimulation with the parasites led to an increase in both IL‐10 and TNF‐α. These results highlight the importance of studying B‐1 CDP cells as phagocytic cells that can participate and contribute to immunity to parasites.     

The Maternal Syndrome of Preeclampsia: A forme fruste of the Systemic Inflammatory Response Syndrome

Preeclampsia is a pregnancy-specific condition, and can be considered to have two component syndromes: maternal, characterized by hypertension and proteinuria, and fetal, manifested by intrauterine growth restriction (IUGR). Maternal deaths due to severe preeclampsia most commonly follow the onset of neutrophil-mediated complications, hepatocellular necrosis and the acute respiratory distress syndrome (ARDS). Hepatocellular necrosis and ARDS are both features of the systemic inflammatory response syndrome (SIRS). Preeclampsia may persist, often deteriorating transiently, following the delivery of the placenta, much as SIRS persists following the resolution of trauma, burns or sepsis. In both conditions there is a systemic response with inflammatory mediator release, endothelial cell dysfunction, a hyperdynamic state, end organ hypoperfusion, and neutrophil activation, resulting in the clinical syndromes. Both preeclampsia and SIRS result from differential responses to initiating factors. Preeclampsia results from incomplete placentation, which also underlies the development of intrauterine growth restriction in isolation (without preeclampsia). Similarly, sepsis, trauma and burns also occur in patients who have unremarkable recoveries rather than developing SIRS. Is preeclampsia a form of SIRS?

     

Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP

Aims/hypothesis  Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells. Methods  Freshly isolated monocytes were incubated with a range of secretions for 1 h and then stimulated with lipopolysaccharides (range 0–100 ng/ml) or lipoteichoic acid (range 0–5 μg/ml) for 18 h. The expression of cell surface molecules, cytokine and chemokine levels in culture supernatants, cell viability, chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured. Results  Maggot secretions dose-dependently inhibited production of the pro-inflammatory cytokines TNF-α, IL-12p40 and macrophage migration inhibitory factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell surface receptors involved in pathogen recognition remained unaffected by secretions. In addition, maggot secretions altered the chemokine profile of monocytes by downregulating macrophage inflammatory protein-1β and upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless, chemotactic responses of monocytes were inhibited by secretions. Furthermore, maggot secretions did not affect phagocytosis and intracellular killing of S. aureus by human monocytes. Finally, secretions induced a transient rise in the intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited the effects of secretions. Conclusions/interpretation  Maggot secretions inhibit the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent mechanism. Regulation of the inflammatory processes by maggots contributes to their beneficial effects on chronic wounds.     

Effects of Bioreactor‐Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients

A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non‐Oxy group). The overall in‐hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non‐Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells.     

Acute-on-chronic Liver Failure

Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.     

TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in immune thrombocytopenic purpura

Objectives: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti‐platelet antibodies induce platelet destruction owing to an imbalanced immune response. Several studies have established that B cells play an important role in the production of anti‐platelet antibodies and that dendritic cells (DC) are professional antigen‐presenting cells of the immune system that may lead to the development of autoantibody through B cells. We aimed at investigating the role of B cells and DC in the pathogenesis of ITP through B‐lymphocyte stimulator (BlyS) and toll‐like receptor 7 (TLR7) signals. Methods: Twenty‐two patients with ITP and 20 healthy controls were enrolled in this study. Serum BlyS, its mRNA and TLR7 mRNA were measured using ELISA kits or RT‐PCR, and CD14⁺ or CD19⁺ monocytes were investigated for the pathogenesis of ITP with in vitro culture systems. Results: We demonstrated that serum BlyS levels in patients with ITP were significantly higher than those in healthy controls and that there was a positive correlation between serum BlyS levels and glycoprotein‐specific antibody levels in patients with ITP. We found that TLR7 regulates dendritic cell‐dependent B‐cell responses through BlyS in patients with ITP. Dendritic cells stimulated with R848 (TLR7 ligand) are able to produce vast amounts of BlyS, which is crucial for B‐cell survival, proliferation and differentiation, and increase anti‐platelet antibodies production in in vitro coculture systems. Conclusions: These findings provide new insights into the pathogenesis of ITP by which TLR7 regulates DC‐dependent B‐cell responses through BlyS.