scholarly journals CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
L. Krabbendam ◽  
B. A. Heesters ◽  
C. M. A. Kradolfer ◽  
N. J. E. Haverkate ◽  
M. A. J. Becker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Nk Cells ◽  
Lymphoid Cells ◽  
Healthy Donors ◽  
Cytotoxic Molecules ◽  
Cytotoxic Molecule ◽  
Definition Of ◽  
Two Populations ◽  
Cytotoxic Effector

AbstractPhenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn’s disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn’s disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn’s disease patients and may play a role in the pathology of the disease.

scholarly journals STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Tang ◽  
Sanda A. Tan ◽  
Atif Iqbal ◽  
Jian Li ◽  
Sarah C. Glover
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Tyrosine Phosphorylation ◽  
Innate Lymphoid Cells ◽  
Immune Defense ◽  
Lymphoid Cells ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
Innate Effector

Crohn’s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele “A” with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 “A” risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

scholarly journals The orphan nuclear receptor RORα and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn’s disease

2016 ◽  
Vol 1 (3) ◽  
pp. eaaf8864-eaaf8864 ◽  
Author(s):  
Bernard C. Lo ◽  
Matthew J. Gold ◽  
Michael R. Hughes ◽  
Frann Antignano ◽  
Yanet Valdez ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mouse Model ◽  
Nuclear Receptor ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Orphan Nuclear Receptor ◽  
Group 3

scholarly journals L’ALTRA PARTE DI NOI – IL MICROBIOMA UMANO

2013 ◽  
Author(s):  
Paolo Landini
Keyword(s):  
Crohn’S Disease ◽  
Immune System ◽  
Crohn's Disease ◽  
Beneficial Effect ◽  
Human Microbiota ◽  
Pathological Conditions ◽  
Beneficial Microorganisms ◽  
Potential Impact ◽  
Definition Of

The importance of microorganisms associated with man, the so-called “human microbiota” has become increasingly clear from recent scientific studies. Although it has been known for many years that some microorganisms might have a beneficial effect on processes such as digestion or on the immune system, the specific mechanisms of these phenomena have never been thoroughly studied. However, in recent years the prevalence of either beneficial microorganisms or harmful bacteria, even though not strictly pathogenic, has been associated with pathological conditions such as obesity, Crohn’s disease, atherosclerosis, and other diseases in which a bacterial component had never been implicated. In this report, I describe the main concepts related to the definition of microbiome and the potential impact of studying the mechanisms of man-microbiome interaction on the treatment of several illnesses.

scholarly journals Crohn’s Disease Patients in Remission Display an Enhanced Intestinal IgM+ B Cell Count in Concert with a Strong Activation of the Intestinal Complement System

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 78 ◽  
Author(s):  
Sophie Preisker ◽  
Ann-Kathrin Brethack ◽  
Arne Bokemeyer ◽  
Dominik Bettenworth ◽  
Christian Sina ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Complement System ◽  
Expression Patterns ◽  
Critical Role ◽  
Mucosal Immune Response ◽  
Immunoglobulin M ◽  
Complement Components ◽  
Activation Pathways ◽  
Definition Of

Inflammatory bowel disease (IBD) is an umbrella term that comprises Crohn’s disease (CD) and ulcerative colitis (UC). Both entities are characterized by a disturbed mucosal immune response and an imbalance of intestinal microbiota composition. The complement system (C) plays a critical role in the detection, and clearance of bacteria and dysregulation of single complement components has been linked to IBD. Here, we asked if the C contributes to distinct subtypes of inflammation observed in CD and UC. We performed systematical expression analyses of the intestinal C in IBD patients and controls. Immunohistochemistry or immunoblot experiments were performed to verify qPCR data. Activity of the three activation pathways of C was studied in sera samples. In CD patients a strong upregulation of the C was observed enabling the definition of unique expression patterns being associated either with remission or active disease. These data were reflected by an enhanced C activation in sera and fecal samples. An excessive mucosal presence of immunoglobulin M (IgM) and CR2/CD21 positive B cells in concert with decreased fecal IgA level was identified in CD patients in remission. These findings point to an exacerbated induction of the intestinal C that may potentially be involved in the etiology of CD.

scholarly journals P049 Lewis score: a useful tool for the diagnosis but not for the definition of prognosis in suspected Crohn's disease

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S102-S103
Author(s):  
M. Silva ◽  
H. Cardoso ◽  
A. Peixoto ◽  
M. Marques ◽  
E. Rodrigues-Pinto ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Definition Of

Sa1868 NK Cells Are Biologic and Biochemical Target of 6-Mercaptopurine in Crohn's Disease Patients

2016 ◽  
Vol 150 (4) ◽  
pp. S385
Author(s):  
Susy Yusung ◽  
Dermot McGovern ◽  
Venu Lagishetty ◽  
Lin Lin ◽  
Jonathan Braun
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Nk Cells

scholarly journals Molecular definition of group 1 innate lymphoid cells in the mouse uterus

2018 ◽  
Author(s):  
Iva Filipovic ◽  
Laura Chiossone ◽  
Paola Vacca ◽  
Russell S Hamilton ◽  
Tiziano Ingegnere ◽  
...  
Keyword(s):  
Nk Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Memory Cells ◽  
Mouse Uterus ◽  
Protein Ubiquitination ◽  
Reproductive Life ◽  
Definition Of ◽  
Molecular Patterns ◽  
Group 1

ABSTRACTDetermining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.

scholarly journals Anti–GM-CSF autoantibodies promote a “pre-diseased” state in Crohn’s Disease

2021 ◽  
Author(s):  
Arthur Mortha ◽  
Romain Remark ◽  
Diane Marie Del Valle ◽  
Ling-Shiang Chuang ◽  
Zhi Chai ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Onset ◽  
Myeloid Cell ◽  
Lymphoid Cells ◽  
Transcriptional Analysis ◽  
Immune Homeostasis ◽  
Cell Axis ◽  
Gm Csf ◽  
Immune Balance

AbstractBackground & AimsAnti–GM-CSF autoantibodies (aGMAb) are detected in ileal Crohn’s Disease (CD) patients. Their induction and mode of action impacting homeostasis during, or prior to disease are not well understood. We aimed to investigate the underlying mechanisms leading to the induction of aGMAb, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as predictive biomarker for complicated CD.MethodsUsing longitudinally collected sera from active component US personnel, we characterize naturally occurring aGMAb in a subset of CD patients years before disease onset. We employed biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD years prior to diagnosis.ResultsNeutralizing aGMAb are specific to posttranslational glycosylations on GM-CSF, detectable years prior to diagnosis, and associated with complicated CD at presentation. Glycosylation and production of GM-CSF change in CD patients, altering myeloid homeostasis and destabilizing group 3 innate lymphoid cells. Perturbations in immune homeostasis precede the inflammation and are detectable in the non-inflamed CD mucosa of patients presenting with anti-GM-CSF autoantibodies.ConclusionsAnti-GM-CSF autoantibodies predict the diagnosis of complicated CD, have unique epitopes, and impair myeloid cell homeostasis across the ILC3-GM-CSF-myeloid cell axis, altering intestinal immune homeostasis long before the diagnosis of disease.

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