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Role of dendritic cells in integrating immune responses to luminal antigens
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Brian L. Kelsall, Maria Rescigno
Study of DCs and macrophages in humans with IBD has been limited largely to inflamed tissue and blood cells, resulting in incomplete characterization of cDCs with nonspecific surface markers. Despite limited information, possible roles of DCs in IBD are shown in Figure 12.7. In humans, activated cDCs accumulate along with macrophages at sites of mucosal inflammation. In Crohn's disease tissue, DCs that express CD83, a glycoprotein associated with DC activation, are present in association with numerous CD83− CD80+ DC-SIGN+ DCs, producing IL-12 and IL-18. The expression of TLR2, TLR4, and CD40 is enhanced in DCs isolated from inflamed mucosa that also overproduce IL-6 and IL-12. Furthermore, mature DCs recruited to the lamina propria form clusters with proliferating T cells in the affected colonic tissue. In ulcerative colitis, an increase in activated CD83+ cells produces macrophage inhibitory factor (MIF), which is thought to contribute to neutrophil recruitment and activation.
Inflammation in Psoriasis and Psoriatic Arthritis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Lesional skin is infiltrated by macrophages and DCs. The DCs show an activated phenotype with expression of CD80, CD83, and CD86. DCs in psoriasis plaques exhibit decreased migration in response to normal stimuli. The CD18 hypomorphic mouse model highlights a critical role for macrophages in the development of psoriasis. Depletion of macrophages reverses psoriasiform lesions in mice models [13].
Genetics, immunology, and pathogenesis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Arthur Kavanaugh, Tristan Boyd
On a histopathologic level, the sequence may occur as follows (see Figure 13.2)65: (1) A genetically susceptible host is exposed to an environmental stimulus (e.g., trauma or infection). (2) Damage to keratinocyte results in release of antigenic material (e.g., antimicrobial peptides) that activates the innate immune response, possibly via binding to Toll-like receptors. (3) Plasmacytoid dendritic cells and other innate cells located in the epidermis are activated and produce proinflammatory cytokines (e.g., IFN-α, TNF-α). (4) These cytokines stimulate myeloid dendritic cells (CD83+) located in the dermis, which subsequently migrate to lymph nodes and present antigen to T cells. (5) T cells are activated by antigen presentation and subsequently proliferate (adaptive immunity). The cytokine milieu favors increased production of Th17 and Th1 cells resulting in an inflammatory response. (6) T cells migrate to the tissues (e.g., skin and synovium) where they perpetuate a chronic inflammatory immune response (e.g., keratinocyte hyperproliferation and synovitis). (7) The overexpression of proinflammatory cytokines results in activation of transcription factors and upregulation of proinflammatory genes. (8) A self-sustaining loop results in a chronic systemic inflammatory process.
Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy
Published in Expert Opinion on Investigational Drugs, 2021
DCs function as antigen-presenting cells (APCs) which play an integral role in activation of the adaptive immune response. DCs are broadly categorized into two subsets: classical or conventional DCs (cDCs) and plasmacytoid DCs (pDC). cDCs originate from bone marrow precursors and have potent phagocytic properties [36]. In the TME, DCs activate the T cell response by capturing, processing, and cross-presenting neoantigens. However, tumor cells can transform DCs to an immature, immunosuppressive phenotype [37]. In CCA, infiltration of mature CD83+ DCs correlated with aggregation of CD4+/CD8+ T cells in the peritumoral region [38]. The presence of CD83+ DCs was also associated with improved patient outcomes. In contrast, the presence of CD1a (immature) DCs in the central tumor region is associated with a paucity of CD4+/CD8+ T cells [38]. FcεRI, a high-affinity immunoglobulin E receptor, is employed by DCs for cross presentation and priming of CTLs [39]. There is a significant decrease in FcεRI+ monocytes and DCs in the peripheral blood of patients with CCA [40]. These findings indicate that DCs are dysfunctional in CCA and unable to restrain tumor progression.
High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects
Published in Platelets, 2019
Mervat A M Youssef, Eman Salah Eldeen, Khalid I Elsayh, Samaher F Taha, Mohamed Gamil M Abo-Elela
CD83 is a maturation marker for DCs that can modulate the immune response by activating DC via sending co-stimulatory signals for stimulation of naive and memory T cells [40]. DXM downregulated the CD83 expression on DCs and inhibit IL-12p70, TNF-α, especially IFN-γ [37]. DXM reduced expression of CD83 when incubated with immature DCs and reduced the DC ability to stimulate allogeneic T cell proliferation in proportion to the level of CD14+, CD83 + cells in the population. CD83 cells, from patients treated with DXM, retained IL-12 production and the capability to stimulate the allogeneic T cell proliferation [35]. In the current study, ITP children exhibited a reduction in CD83 expression after a short course of HD-DXM, which may explain the acute upgrading in the platelet level.
CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy
Published in OncoImmunology, 2018
Sadia Zafar, Suvi Sorsa, Mikko Siurala, Otto Hemminki, Riikka Havunen, Victor Cervera-Carrascon, João Manuel Santos, Hongjie Wang, Andre Lieber, Tanja De Gruijl, Anna Kanerva, Akseli Hemminki
To investigate mechanism-of-action, four mice from each group were euthanized one week after the last administration of DCs. Analysis of the microenvironment revealed robust upregulation of DC maturation markers CD83, CD80, and CD86 in tumors treated with triple therapy (Figures 5A-C). Moreover, infiltration of significantly high levels of B and T lymphocytes in the same groups were also observed (Figures 5D and 5E). The immune modulation of the tumor microenvironment towards Th1 phenotype was further confirmed through the presences of high levels of TNF alpha, IFN gamma, IL2, IL12, granzyme B and IL6 in the same groups (Supplementary Figure 3); In summary, our findings suggest that expression of CD40L in the tumor induces maturation of DCs, leading to activation of adaptive immune response against the tumor.