The Role of Dendritic Cells, B Cells, and M Cells in Gut-Oriented Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

Download Full-text

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

10.21203/rs.3.rs-52170/v3 ◽

2020 ◽

Author(s):

Xiaoyi Li ◽

Qifan Zhang ◽

Wanyue Zhang ◽

Guofu Ye ◽

Yanchen Ma ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

B Cells ◽

Hepatitis B ◽

Immune Responses ◽

Cd4 T Cells ◽

Hbv Infection ◽

Follicular Dendritic Cells ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

Download Full-text

Immunosuppressive Mechanisms of Regulatory B Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.611795 ◽

2021 ◽

Vol 12 ◽

Author(s):

Diego Catalán ◽

Miguel Andrés Mansilla ◽

Ashley Ferrier ◽

Lilian Soto ◽

Kristine Oleinika ◽

...

Keyword(s):

B Cells ◽

Immune Responses ◽

Metabolic Diseases ◽

Inflammatory Responses ◽

Surface Proteins ◽

Regulatory B Cells ◽

Cell Surface Proteins ◽

The Past ◽

And Function

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

Download Full-text

P01.11 Role of exosomes as promotors or biomarkers to study activation of leukemia-derived dendritic cells (DCleu)-mediated antileukemic activation of adaptive and innate immune-reactive cells against AML-blasts

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-itoc7.24 ◽

2020 ◽

Vol 8 (Suppl 2) ◽

pp. A13.2-A14

Author(s):

L Li ◽

V Mussack ◽

E Pepeldjiyska ◽

A Hartz ◽

A Rank ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Healthy Volunteers ◽

Information Transfer ◽

Immune Monitoring ◽

Lymphocyte Culture ◽

Innate Immune ◽

Proliferating Cells ◽

Continuous Increase

BackgroundAntileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. Exosomes are small (30–150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. Their involvement in nearly all aspects of malignant transformation has generated much interest in their biology, mechanisms responsible for information transfer and their role in immune-surveillance as well as -escape.Exosomes secreted by dendritic cells (DCs) have been shown to allow efficient activation of T lymphocytes, displaying potential as promoters of adaptive immune responses.Materials and Methods1)DC/DCleu-culture of blast containing AML patients’ whole blood (WB) (n=10) and of healthy volunteers(n=8) with kits, T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB, functional blast-cytotoxicity and, leukemia-specificity assays (Degranulation/intracellular cytokine-assays), Flowcytometric evaluation of blast-,DC- and lymphocyte composition before or after cultures. 2)Exosomes were isolated by immunoaffinity from serum, DC- and MLC-culture supernatants of 3 AML patients and 3 healthy volunteers. Exosomes were negatively stained and characterized by transmission electron microscopy (TEM). Fluorescence nanoparticle tracking analysis (fNTA) was performed to determine exosomal size and -concentration. Obtained results were compared in AML and healthy volunteers.ResultsAddition of kitM to blast-containing WB significantly increased frequencies of mature DC/DCleu and their subtypes compared to untreated WB without induction of blasts’ proliferation. Immune monitoring showed a continuous increase ofactivated/proliferating cells of the adaptive and innate immune system after Tcell-enriched MLC using kitM pretreated vs -untreated WB, suggesting a production/activation of (potentially leukemia-specific) cells after kit-stimulation. Moreover kit-pretreated WB regularly and significantly improved provision, activation as well as antileukemic and leukemia-specifically directed immune reactive cells after MLC. TEM showed exosome-like structures with a typically cup-shaped appearance without any differences between healthy and AML samples. fNTA revealed average vesicle sizes of 177±23 nm (healthy) and 178±17 nm (AML). Higher levels of EVs were detectable in AML samples compared to healthy controls in serum and after DC-culture, but lower levels after MLC independent of culture conditions.Interestingly, the number of EVs increased during cultivation of DC of AML and healthy samples, but not in AML-derived MLC samples.ConclusionsWe will provide data in AML patients and healthy volunteers about a potential role of DCs- and MLC-derived exosomes as biomarkers in immune responses, malignant progression or as potential therapeutic targets for AML patients.Disclosure InformationL. li: None. V. Mussack: None. E. Pepeldjiyska: None. A. Hartz: None. A. Rank: None. C. Schmid: None. E. Özkaya: None. S. Ugur: None. M. Pfaffl: None. H. Schmetzer: None.

Download Full-text

Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽

10.3390/genes11030323 ◽

2020 ◽

Vol 11 (3) ◽

pp. 323 ◽

Cited By ~ 1

Author(s):

Guoying Wang ◽

Xianghui Li ◽

Lei Zhang ◽

Abualgasim Elgaili Abdalla ◽

Tieshan Teng ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune Responses ◽

Critical Role ◽

Innate Immune ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Th2 Responses ◽

Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

Download Full-text

B-1a B Cells that Link the Innate and Adaptive Immune Responses Are Lacking in the Absence of the Spleen

Journal of Experimental Medicine ◽

10.1084/jem.20011140 ◽

2002 ◽

Vol 195 (6) ◽

pp. 771-780 ◽

Cited By ~ 185

Author(s):

Hedda Wardemann ◽

Thomas Boehm ◽

Neil Dear ◽

Rita Carsetti

Keyword(s):

B Cells ◽

Immune Responses ◽

B Cell ◽

Innate Immune ◽

Streptococcal Infections ◽

Wild Type ◽

Adaptive Immune ◽

Encapsulated Bacteria ◽

Increased Susceptibility

Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

Download Full-text