scholarly journals Case Report: Regulatory T Cell-Independent Induction of Remission in a Patient With Collagenous Colitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hajime Honjo ◽  
Tomohiro Watanabe ◽  
Mizuki Tomooka ◽  
Takuya Matsubara ◽  
Masashi Kono ◽  
...  
Keyword(s):  
T Cells ◽  
Lamina Propria ◽  
Colonic Mucosa ◽  
Inflammatory Responses ◽  
Collagenous Colitis ◽  
Pathological Examination ◽  
Surface Epithelium ◽  
Inflammatory Disorder ◽  
Independent Manner ◽  
Chronic Inflammatory Disorder

Collagenous colitis (CC), a prototypical microscopic colitis, is a chronic inflammatory disorder of the colon. The diagnosis of CC depends on the pathological examination. The colonic mucosa of patients with CC is characterized by the presence of a substantially thickened collagen band (>10μm) under the surface epithelium. In addition, intraepithelial and lamina propria lymphocytes are markedly increased in patients with CC. However, the roles played by the lymphocytes accumulating in the colonic mucosa of patients with CC are poorly defined. Recent studies indicate that T cells infiltrating the colonic mucosa of patients with CC are mainly represented by CD4+ T cells, CD8+ T cells, and forkhead box P3 (FOXP3)+ regulatory T cells (Tregs). Given that activation of CD4+/CD8+ T cells and FOXP3+ Tregs usually mediates pro-inflammatory and anti-inflammatory responses, respectively, alterations in the colonic numbers of these adaptive T cells might be related to the resolution of colitis in patients with CC. We determined alterations in the composition of colonic T cells by extensive immunohistochemical (IHC) analyses in a case of CC successfully treated with budesonide and metronidazole. Colonic lamina propria immune cells mainly comprised CD3+ T cells, CD4+ T cells, CD8+ T cells, CD68+ macrophages, and FOXP3+ Tregs, but not CD20+ B cells or myeloperoxidase (MPO)+ granulocytes in the active phase. During remission, the numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages did not change significantly in the colonic lamina propria, whereas FOXP3+ Tregs were markedly decreased, suggesting that induction of remission was achieved in a Treg-independent manner. Thus, our study indicates that accumulation of FOXP3+ Tregs in the colonic mucosa of patients with CC might be a counter-regulatory mechanism reflecting persistent inflammation and that induction of remission might be achieved without activation of Tregs.

scholarly journals Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Vuerich ◽  
Na Wang ◽  
Ahmadreza Kalbasi ◽  
Jonathon J. Graham ◽  
Maria Serena Longhi
Keyword(s):  
Autoimmune Hepatitis ◽  
Immune Regulation ◽  
Th17 Cells ◽  
Inflammatory Responses ◽  
Calcineurin Inhibitors ◽  
Inflammatory Disorder ◽  
Disease Relapse ◽  
Regulatory Cells ◽  
Chronic Inflammatory Disorder ◽  
Therapeutic Tools

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools.

scholarly journals Natural killer T cells in lipoprotein metabolism and atherosclerosis

2011 ◽  
Vol 106 (11) ◽  
pp. 814-819 ◽  
Author(s):  
Godfrey Getz ◽  
Paul VanderLaan ◽  
Catherine Reardon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cell Receptor ◽  
Nkt Cells ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Invariant Nkt Cells ◽  
Adaptive Immune ◽  
Natural Killer T

SummaryCells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined.

scholarly journals Interleukin-23 drives innate and T cell–mediated intestinal inflammation

2006 ◽  
Vol 203 (11) ◽  
pp. 2473-2483 ◽  
Author(s):  
Sophie Hue ◽  
Philip Ahern ◽  
Sofia Buonocore ◽  
Marika C. Kullberg ◽  
Daniel J. Cua ◽  
...  
Keyword(s):  
T Cell ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune ◽  
Proinflammatory Responses ◽  
Interleukin 23 ◽  
Immune Pathology ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We have used two complementary models of IBD to examine the roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal inflammation. Our results clearly show that IL-23, but not IL-12, is essential for the induction of chronic intestinal inflammation mediated by innate or adaptive immune mechanisms. Depletion of IL-23 was associated with decreased proinflammatory responses in the intestine but had little impact on systemic T cell inflammatory responses. These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD.

scholarly journals Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xueyan Ding ◽  
Peng Bin ◽  
Wenwen Wu ◽  
Yajie Chang ◽  
Guoqiang Zhu
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Cells ◽  
Bowel Disease ◽  
Kynurenine Pathway ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Bowel ◽  
Treg Differentiation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from the homeostasis imbalance of intestinal microenvironment, immune dysfunction, environmental and genetic factors, and so on. This disease is associated with multiple immune cells including regulatory T cells (Tregs). Tregs are a subset of T cells regulating the function of various immune cells to induce immune tolerance and maintain intestinal immune homeostasis. Tregs are correlated with the initiation and progression of IBD; therefore, strategies that affect the differentiation and function of Tregs may be promising for the prevention of IBD-associated pathology. It is worth noting that tryptophan (Trp) metabolism is effective in inducing the differentiation of Tregs through microbiota-mediated degradation and kynurenine pathway (KP), which is important for maintaining the function of Tregs. Interestingly, patients with IBD show Trp metabolism disorder in the pathological process, including changes in the concentrations of Trp and its metabolites and alteration in the activities of related catalytic enzymes. Thus, manipulation of Treg differentiation through Trp metabolism may provide a potential target for prevention of IBD. The purpose of this review is to highlight the relationship between Trp metabolism and Treg differentiation and the role of this interaction in the pathogenesis of IBD.

scholarly journals Colonic Mucosa Barrier Defects in Collagenous and Ischemic Colitis

2021 ◽  
Author(s):  
Stratigoula Sakellariou ◽  
Μarina Perdiki ◽  
Kostas Palamaris ◽  
Giorgos Bamias ◽  
Ioanna Delladetsima
Keyword(s):  
Lamina Propria ◽  
Ischemic Colitis ◽  
Colonic Mucosa ◽  
Collagenous Colitis ◽  
High Sensitivity ◽  
Normal Mucosa ◽  
Diagnostic Significance ◽  
Disease States ◽  
Cell Processes ◽  
And Migration

Abstract Aims The subepithelial myofibroblasts (SEMFs) and the subepithelial band of macrophages (SEBM) are major components of the colonic mucosa barrier. Although their role in homeostasis is widely recognized, their contribution to disease states is largely unknown. The aim of the study was to explore histological characteristics of SEMFs and SEBM in collagenous and ischemic colitis.Methods Ten colonic biopsies of collagenous colitis, 10 of ischemic colitis and 10 control biopsies of normal mucosa were examined. SEMFs, SEBM and lamina propria macrophages were identified immunohistochemically by aSMA and CD68 respectively.ResultsIn collagenous colitis, SEMFs were rarely detectable in the collagenous band while in the lower lamina propria cell processes were formed. SEBM was preserved in areas with a collagenous layer up to 20μm. In thicker layers, it was fragmented and gradually disappeared in parallel with engulfment of enlarged macrophages. In the lower lamina propria macrophages were usually increased.In ischemic colitis, rounding, disintegration and extinction of SEMFs constituted successive alterations coinciding with crypt shrinkage and denudation. SEBM displayed total or almost total abolishment in areas with crypt damage and stroma fibrosis but also in sights with minimal changes.ConclusionIn collagenous colitis, alterations of mucosa barrier are related to collagenous layer thickness. SEMFs changes probably reflect derangement of differentiation and migration while SEMB alterations seem to be compensated by macrophage activation and numerical increase in lamina propria. The striking damage of mucosa barrier in ischemic colitis is indicative of its high sensitivity to hypoxia and hypoperfusion. The histological differences between collagenous colitis and ischemic colitis may be proven of differential diagnostic significance.

P158 LOSS OF AUTOTAXIN ALTERS INNATE AND ADAPTIVE IMMUNE MECHANISM AND PROMOTES SPONTANEOUS COLITIS IN IL10-KO MICE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S33-S33
Author(s):  
Su Jin Kim ◽  
Cody Howe ◽  
Jonathon Mitchell ◽  
Eunok Im ◽  
Sang Rhee
Keyword(s):  
T Cells ◽  
Complex Formation ◽  
Lipid Rafts ◽  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Bacterial Load ◽  
Serum Samples ◽  
Adaptive Immune

Abstract Background & Aims Autotaxin (Atx) is a secreted enzyme converting lysophosphatidylcholine (LPC) and sphingosyl-phosphorylcholine into lysophosphatidic acid and sphingosine 1-phosphate, respectively. Given the high affinity of LPC to cholesterol and the enrichment of cholesterol and sphingolipids in lipid rafts wherein LPS sensor Toll-like receptor 4 (TLR4) and its co-receptor CD14 reside, we hypothesized that Atx deficiency inhibits TLR4-mediated innate and adaptive immunity; thereby, accelerating the susceptibility to microbe-induced intestinal inflammation. Method We generated myeloid cell lineage-restricted Atx-knockout (ko) mice (AtxdME/dME) to study TLR4-mediated immune and inflammatory responses and investigated LPS-receptor complex formation through fluorescence resonance energy transfer technique, confocal microscopy, and flow cytometry. Lamina propria CD4+ T cells and bacterial load in the intestinal mucosa were examined. An impact of Atx deficiency in inflammatory bowel diseases (IBD) was investigated using AtxdME/dME;Il10-/- mice that have both Atx-deletion in myeloid cells and a global Il10 deletion. We examined the serum samples from IBD patients. Results With peritoneal macrophages from AtxdME/dME mice, we identified that Atx-ko disrupted the integrity of lipid rafts at the plasma membrane, resulting in the inhibition of TLR4 complex formation. Accordingly, the recruitment of adaptor molecules to TLR4 was suppressed, and TLR4-mediated responses were substantially reduced in Atx-ko macrophages. TLR4-induced innate immunity such as phagocytosis was attenuated in Atx-ko macrophages. The activation of CD4+ effector T cells and regulatory T cells was diminished in the lamina propria lymphocytes of AtxdME/dME mice compared to that of Atx+/+ littermates. Consequently, AtxdME/dME mice had a higher bacterial prevalence in the intestinal mucosa compared to controls. Just like the notion that commensal microbes translocated from the lumen into the intestinal mucosa can elicit spontaneous colitis in Il10-/- mice, combining AtxdME/dME with Il10-/- mice (AtxdME/dME; Il10-/-) did accelerate spontaneous colitis development. AtxdME/dME; Il10-/- mice had gross inflammation occurring throughout the colon, massive neutrophil infiltration and necrosis in the colonic mucosa, and increased mortality (Log-rank P=0.0046), while Atx+/+;Il10-/- littermates are normal. Notably, ATX serum protein level was lower in UC (n=26) and CD (n=34) patients compared to the level in normal subjects (n=26) (P<0.001), indicating an association of reduced ATX levels with the intestinal inflammation. Conclusions Collectively, we found that Atx deficiency suppresses TLR4-mediated innate and adaptive immune mechanisms; thereby accelerating the susceptibility to microbe-induced gut inflammation.

scholarly journals AnIn VitroModel to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4+T Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Ashok Kumar Kumawat ◽  
Nils Nyhlin ◽  
Anna Wickbom ◽  
Curt Tysk ◽  
Johan Bohr ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Colonic Mucosa ◽  
Collagenous Colitis ◽  
Soluble Factors ◽  
Enhanced Production ◽  
Anti Inflammatory ◽  
The Impact

Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established anin vitromodel to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4+T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1βand the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4+T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, ourin vitromodel reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines.

scholarly journals The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Maedeh Radandish ◽  
Parvin Khalilian ◽  
Nafiseh Esmaeil
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Myeloid Cell ◽  
Therapeutic Agents ◽  
Vital Role ◽  
Inflammatory Disorder ◽  
The Impact

Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain’s parenchyma, known as microglia and monocyte-derived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.

scholarly journals Survivin and Programmed Death Ligand-1 as Possible Players in the Pathogenesis of Ulcerative Colitis: An Immunohistochemical Study

2020 ◽  
Vol 8 (A) ◽  
pp. 646-651
Author(s):  
Reham Shehab El Nemr Esmail ◽  
Eman Hassan Abdelbary
Keyword(s):  
Ulcerative Colitis ◽  
Lamina Propria ◽  
Immunohistochemical Study ◽  
Control Group ◽  
Inflammatory Disorder ◽  
Immunohistochemical Expression ◽  
Chronic Inflammatory Disorder ◽  
Programmed Death ◽  
Mucosal Cells ◽  
Inflammatory Bowel

BACKGROUND: Ulcerative colitis (UC) is a relapsing chronic inflammatory disorder, with many catastrophic complications. The pathogenesis of UC is not yet well understood. Exploring the exact immunologic pathogenesis of UC may eventually offer new therapeutic options. AIM OF THE WORK: In this study, we proposed that survivin and programmed death ligand (PDL1) may have roles in the pathogenesis of UC. MATERIALS AND METHODS: The study examined the immunohistochemical expression of both markers in the colonic epithelial cells and lamina propria in 43 cases of UC and 43 cases of non-specific chronic colitis (non-inflammatory bowel disease colitis). RESULTS: The results uncovered that both survivin and PDL1 expression were significantly expressed in the colonic lamina propria cells in UC cases in comparison to colitis cases (p < 0.001). On the other hand, the expression of PDL1 was shown to be lost in the colonic mucosal cells in UC cases when compared to cases of the control group (p < 0.05). CONCLUSION: The study, therefore, concluded that both survivin and PDL1 may play an important role in the UC pathogenesis and hence may be a novel interest in new therapeutic trends.

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