Curcumin: A Dietary Phytochemical for Targeting the Phenotype and Function of Dendritic Cells

Abstract

: Dendritic cells (DCs) are the most powerful antigen-presenting cells which link the innate and adaptive immune responses. Depending on the context DCs initiate the immune responses or contribute to immune tolerance. Any disturbance in their phenotypes and functions may initiate inflammatory or autoimmune diseases. Hence, dysregulated DCs are the most attractive pharmacological target for the development of new therapies aiming at reducing their immunogenicity and at enhancing their tolerogenicity. Curcumin is the polyphenolic phytochemical component of the spice turmeric with a wide range of pharmacological activities. It acts in several ways as a modulator of DCs and converts them into tolerogenic DCs. Tolerogenic DCs possess anti-inflammatory and immunomodulatory activities that regulate the immune responses in health and disease. Curcumin by blocking maturation markers, cytokines and chemokines expression, and disrupting the antigen-presenting machinery of DCs render them non- or hypo-responsive to immunostimulants. It also reduces the expression of co-stimulatory and adhesion molecules on DCs and prevents them from both migration and antigen presentation but enhances their endocytosis capacity. Hence, curcumin causes DCs-inducing regulatory T cells and dampens CD4+ T helper 1 (Th1), Th2, and Th17 polarization. Inhibition of transcription factors such as NF-κB, AP-1, MAPKs (p38, JNK, ERK) and other intracellular signaling molecules such as JAK/STAT/SOCS provide a plausible explanation for most of these observations. In this review, we summarize the potential effects of curcumin on the phenotypes and functions of DCs as the key players in orchestration, stimulation, and modulation of the immune responses.

The effect of Curcumin on multi-level immune checkpoint blockade and T cell dysfunction in head and neck cancer

“…Although, the immune-modulatory actions of Curcumin have been shown in a wide range of in ammatory and autoimmune diseases such as arthritis, colitis and hepatitis, its immunomodulatory capacity in the TME has emerged relatively recently. Research has shown that Curcumin not only enhances tumor antigen-speci c T cells via reversal of tumor-induced immunosuppression but also enhances cytotoxic T cells by acting directly on immune cell dysfunction, which is one of the major mechanisms of tumor escape from immune surveillance via the signal transducer and activator of transcription 3 and nuclear factor kappa B (NF-kB) signaling pathways [23,43,44]. Lim et al [45]showed inhibition of in ammation-mediated PD-L1 expression by Curcumin, and Liao et al [46] showed decreased PD-L1 expression following immunosuppression in cell populations, such as Tregs and myeloid-derived suppressor cells, in a murine oral cancer model after Curcumin treatment.…”

Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials

“…The natural spice curcumin has received recent attention in treating diseases involving perturbations of the immune system and inflammation responses, such as COVID-19 [12][13][14][15]. Curcumin and other curcuminoids are the main bioactive ingredients of turmeric (Curcuma longa).…”

New Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases

“…Moreover, intervening in the regulatory network of CCR7 also shows great prospect for inflammatory disease remission. Cyclosporin A, triptolide, and curcumin were found to inhibit LPS-triggered upregulation of COX-2, PGE2, NF-κB, and AP-1 along with subsequent CCR7 expression, thus impairing the chemotaxis of DCs to CCL19/21 and motivating tolerance in diseases (Chen et al, 2004;Liu et al, 2007;Rahimi et al, 2021). Semaphorin 3E may regulate IRF4 to alter CCR7 levels and benefit allergic airway hyperresponsiveness (Movassagh et al, 2021).…”