Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

Park, Hui-Won; Park, Sun-Hee; Jo, Hyeon-Ju; Kim, Taegyu; Lee, Jeong Hyun; Kang, Seung Goo; Jang, Young‐Saeng; Kim, Pyeung-Hyeun

doi:10.4110/in.2020.20.e38

Cited by 3 publications

(5 citation statements)

References 38 publications

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“…Single cell suspensions of spleen and BM were prepared and assayed by FACS as described ( 42 ). To detect cytokine expression, CD4 + T cells were stimulated with 20 ng/ml PMA and 1 μM ionomycin (both from Sigma-Aldrich) in the presence of Golgi-stop reagent (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations of total IgG and total IgM Abs were measured using ELISA kits (Bethyl Laboratories and Alpha Diagnostic International, respectively), according to the manufacturer's protocols. The titers of serum anti-dsDNA IgG Ab and numbers of anti-dsDNA IgG-secreting cells in spleens and BM were determined as described previously ( 42 ). To measure levels of BAFF in sera and in supernatants of SDMCs cultured with 2 μg/ml LPS for 48 h, samples were assayed using Duoset ELISA kit (R&D Systems).…”

Section: Methodsmentioning

confidence: 99%

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An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

et al. 2021

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Splenic long-lived plasma cells are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b+Gr-1+ myeloid cells (SDMCs) underpins the accumulation of splenic long-lived plasma cells in a lupus-prone model named sanroque. We found that SDMCs were progressively accumulated in sanroque mice from the early clinical phase. Transcriptome profiles revealed that SDMCs have a predominant shift toward an inflammatory phenotype relative to the bone marrow-derived counterparts and are distinct from neutrophils and monocytes. SDMCs were expanded in situ via splenic extramedullary myelopoiesis under the proinflammatory cytokine milieu during lupus progression. SDMCs promoted the development of IFN-γ-secreting Th1 and follicular helper T cells, thereby licensing CD4+ T cells to be pathologic activators of SDMCs and plasma cells. SDMCs also directly promoted the survival of plasma cells by providing B-cell activating factor of the TNF family. The frequency of SDMCs correlated with that of splenic long-lived plasma cells. Selective depletion of CD11b+Gr-1+ cells reduced autoantibody production in sanroque mice. Thus, our findings suggest that SDMCs expanded in situ establish a positive feedback loop with CD4+ T cells, leading to accumulation of long-lived plasma cells which exacerbates lupus autoimmunity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

et al. 2021

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“…LF supplementation enhances the expression of CD80, CD83, and CD86, and the production of proinflammatory cytokines of monocyte-derived dendritic cells, which indicate this type of cell maturation ( 124 ). Furthermore, LF effectively causes DCs to be tolerogenic by suppressing CD4 + T cells proliferation and enhancing Treg cell differentiation from CD4 + T cells in the colon, when compared with the DSS group ( 37 , 38 ). Recently, LF has been reported to promote the macrophage shift from inflammatory to tolerogenic phenotype, which is key for tissue homeostasis ( 133 ).…”

Section: Functional Role Of Lactoferrin In Inflammatory Bowel Diseasementioning

confidence: 98%

“…Furthermore, the LF treatment reduced the secretion and gene expression of tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3) signaling pathway activation, both in cultured and Crohn-derived intestinal cells ( 29 , 33 – 36 ). It was noted that LF effectively causes dendritic cells (DCs) and macrophages to be tolerogenic phenotype by inhibiting the proliferation of CD4 + T cells and enhancing Treg cell differentiation from CD4 + T cells in the colon, which is key for tissue homeostasis ( 37 , 38 ).…”

Section: Introductionmentioning

confidence: 99%

The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

et al. 2021

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Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is one of the main types of intestinal inflammatory diseases with intestine mucosal immune disorder. Intestine mucosal immune system plays a remarkable and important role in the etiology and pathogenesis of IBD. Therefore, understanding the intestine mucosal immune mechanism is a key step to develop therapeutic interventions for IBD. Intestine mucosal immune system and IBD are influenced by various factors, such as inflammation, gut permeability, gut microbiota, and nutrients. Among these factors, emerging evidence show that nutrients play a key role in inflammation activation, integrity of intestinal barrier, and immune cell modulation. Lactoferrin (LF), an iron-binding glycoprotein belonging to transferrin family, is a dietary bioactive component abundantly found in mammalian milk. Notably, LF has been reported to perform diverse biological functions including antibacterial activity, anti-inflammatory activity, intestinal barrier protection, and immune cell modulation, and is involved in maintaining intestine mucosal immune homeostasis. The improved understanding of the properties of LF in intestine mucosal immune system and IBD will facilitate its application in nutrition, clinical medicine, and health. Herein, this review outlines the recent advancements on LF as a potential therapeutic intervention for IBD associated with intestine mucosal immune system dysfunction. We hope this review will provide a reference for future studies and lay a theoretical foundation for LF-based therapeutic interventions for IBD by understanding the particular effects of LF on intestine mucosal immune system.

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“…The hLf1-11 peptide derived from human lactoferrin (hLf) can inhibit myeloperoxidase, which is a major host defense enzyme found in a variety of white blood cells, which may further decrease the innate immune response (22). Furthermore, hLf has been shown to stimulate the maturation of dendritic cells and recruit various white blood cells (23). Therefore, Lf plays an activating role in innate and adaptive immune responses.…”

Section: Lf Exerts Both Immunostimulatory and Immunomodu Latory Activ...mentioning

confidence: 99%

Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities

Pan

Weng

et al. 2021

Int J Oncol

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Lactoferrin (Lf) is secreted by ectodermal tissue and has a structure similar to that of transferrin. Although Lf seems to be multifunctional, its main function is related to the natural defense system of mammals. The present review aims to highlight the major actions of Lf, including the regulation of cell growth, the inhibition of toxic compound formation, the removal of harmful free radicals and its important role in immune response regulation. Moreover, Lf has antibacterial, antiviral, antioxidant, anticancer and anti-inflammatory activities. In addition, the use of Lf for functionalization of drug nanocarriers, with emphasis on tumor-targeted drug delivery, is illustrated. Such effects serve as an important theoretical basis for its future development and application. In neurodegenerative diseases and the brains of elderly people, Lf expression is markedly upregulated. Lf may exert an anti-inflammatory effect by inhibiting the formation of hydroxyl free radicals. Through its antioxidant properties, Lf can prevent DNA damage, thereby preventing tumor formation in the central nervous system. In addition, Lf specifically activates the p53 tumor suppressor gene. Contents1. Introduction 2. Lf exerts both immunostimulatory and immunomodulatory activities 3. Lf is a natural immune modulator involved in the antitumor response 4. Lf has anticancer effects on tumors of the central nervous system 5. Lf affects tumor progression by exerting anti-bacterial and anti-viral activities 6. Lf has enzyme activity functions 7. Lf plays an extensive role in nanotechnology 8. Conclusion and perspectives

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Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

Cited by 3 publications

References 38 publications

An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities

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