The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models

Steinert, Anna; Linas, Ioannis; Kaya, Berna; Ibrahim, Mohamed; Schlitzer, Andreas; Hrúz, Petr; Radulovic, Katarina; Terracciano, Luigi; Macpherson, Andrew J.; Niess, Jan Hendrik

doi:10.4049/jimmunol.1700350

Cited by 31 publications

(30 citation statements)

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“…1eg). Recently, the role of IL-20 cytokine subfamily has been proposed in tissue remodeling [26], and increased expression of IL-19, -20 and -24 was demonstrated in PBMCs and also in colonic mucosa of adult IBD patients [11,[13][14][15]. It has been suggested that these cytokines may protect the integrity of the inflamed mucosa of patients with IBD.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increased expression of IL-19, IL-20 and IL-24 has been demonstrated in the colonic mucosa and also in peripheral blood mononuclear cells (PBMCs) of patients with inflammatory bowel diseases (IBD) [11][12][13][14][15]. However, to the best of our knowledge, there are no previous data available about the significance of IL-19, IL-20 and IL-24 in CD.…”

Section: Introductionmentioning

confidence: 99%

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Role of IL-24 in the mucosal remodeling of children with coeliac disease

et al. 2020

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Background: Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown. Methods: Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1β, TNF-α, TGF-β and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H 2 O 2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy. Results: We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1β was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H 2 O 2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2. Conclusion: Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of IL-24 in the mucosal remodeling of children with coeliac disease

et al. 2020

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“…Clinical colitis score. Clinical signs of colitis were observed by using the following scores 50 : rectal bleeding: 0-absent, 1-bleeding; rectal prolapses: 0-nil, clear prolapse-mice euthanized; stool consistency: 0-normal, 1-loose stools, 2diarrhea; position: 0-normal movement, 1-reluctance to move, 2-hunched position; appearance of the fur: 0-normal appearance, 1-ruffled fur, 2-spiky fur; weight loss: 0-no loss, 1-body weight loss 0-5%, 2-body weight loss >5-10%, 3-body weight loss >10-15%, 4-body weight loss >15%. Once per day, the blinded investigator observed the animals.…”

Section: Methodsmentioning

confidence: 99%

Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice

et al. 2020

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Comprehensive development is critical for gut macrophages being essential for the intestinal immune system. However, the underlying mechanisms of macrophage development in the colon remain elusive. To investigate the function of branched-chain amino acids in the development of gut macrophages, an inducible knockout mouse model for the branchedchain amino acid transporter CD98hc in CX3CR1 + macrophages was generated. The relatively selective deletion of CD98hc in macrophage populations leads to attenuated severity of chemically-induced colitis that we assessed by clinical, endoscopic, and histological scoring. Single-cell RNA sequencing of colonic lamina propria macrophages revealed that conditional deletion of CD98hc alters the "monocyte waterfall"-development to MHC II + macrophages. The change in the macrophage development after deletion of CD98hc is associated with increased apoptotic gene expression. Our results show that CD98hc deletion changes the development of colonic macrophages.

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“…IL-22 binds to the IL-22 receptor expressed by intestinal epithelial cells to protect the intestine from damage and to support regeneration by inducing the expression of chemokines involved in cellular mobility, facilitating the expression of the antibacterial lectins RegIIIβ and RegIIIγ and inducing the expression of mucins after STAT3 activation ( 5 ). Therefore, the IL-22 receptor is highly expressed in the entire gastrointestinal tract ( 6 , 7 ) (Table 1 ).…”

Section: Expression Of Il-20r Along the Gastrointestinal Tractmentioning

confidence: 99%

The Interleukin-20 Cytokines in Intestinal Diseases

2018

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Autoimmune/inflammatory intestinal diseases, such as Crohn’s disease and ulcerative colitis, infectious gastrointestinal diseases, and gastrointestinal cancers, such as colorectal cancer, are worldwide a significant health problem. Intercellular communication and direct contact with the environment as the microbiota colonizes the gastrointestinal surface facilitates these diseases. Cytokines mediate the intercellular communication to maintain the equilibrium between host and environment and to regulate immune responses. One cytokine family that exchange information between immune cells and epithelial cells is the IL-20 cytokine family which includes the cytokines IL-19, IL-20, IL-22, IL-24, and IL-26. These cytokines share common receptor subunits and signaling pathways. IL-22 is the most intensively studied cytokine within this family in contexts of gastrointestinal disease, but the importance of other family members is more and more appreciated. In this review, the potential function of IL-20 cytokines concerning gastrointestinal conditions is discussed.

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The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models

Cited by 31 publications

References 50 publications

Role of IL-24 in the mucosal remodeling of children with coeliac disease

Role of IL-24 in the mucosal remodeling of children with coeliac disease

Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice

The Interleukin-20 Cytokines in Intestinal Diseases

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