scholarly journals P007 Identification and characterisation of intestine-derived circulating resident memory T cells (ex-Trm) in health and Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S128-S128
Author(s):  
B Rodger ◽  
I Hoti ◽  
H Gordon ◽  
J Lindsay ◽  
A Stagg
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Memory T Cells ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Tissues ◽  
Resident Memory T Cells

Abstract Background Tissue resident memory T cells (Trm) persist in peripheral tissues where they protect against pathogens but can also contribute to inflammatory disease. Recent work shows that Trm can re-enter the circulation and give rise to new effector T cell and Trm populations in secondary tissue sites. Such ‘ex -Trm’ derived from the skin co-express the residency marker CD103 with cutaneous leukocyte antigen (CLA), a marker associated with skin tropism. Many T cells in the human intestine are Trm but it is unknown whether these cells re-enter the circulation; the existence of gut-derived ex-Trm would have important implications for IBD treatment targeting the recruitment of circulating gut-homing cells. Here, we identify a population of blood cells that co-express CD103 and the gut-homing integrin a4b7 and determine how they are changed in IBD. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and patients with active IBD (Crohn’s disease or ulcerative colitis). Cell surface staining and multi-colour flow cytometry were used to identify CD4+ and CD8+ subsets of antigen experienced (CD45RA-) conventional T cells (abTCR+) and determine expression of markers associated with tissue tropism and residency. Results Staining with antibodies to CD103 and b7 integrin were used to define CD103b7+a4b7+ putative gut ex-Trm based on the excess per cell expression of b7 resulting from its contribution to both integrins. A separate CD103b7+a4b7- population defined by 1:1 expression of CD103 and b7 contained CLA+ skin ex-Trm. Gut ex-Trm comprised 0.3% total circulating CD8+ T cells (range 0.02–1.4%), and 1.2% CD4+ T cells (range 0.3–3%). Gut and skin ex-Trm were phenotypically similar; both expressed the residency associated markers CD101 and CD9 but lacked expression of CD69. Gut ex-Trm were phenotypically distinct from both traditional CD103-a4b7+ gut tropic CD45RA- antigen-experienced T cells and naïve T cells; significantly more gut ex-Trm expressed CD101 and CD9 and fewer expressed CD27. The proportion of gut ex-Trm did not differ between heath and IBD. However, the ratio of gut:skin ex Trm was significantly reduced in active Crohn’s disease but not ulcerative colitis indicating a selective reduction in the population derived from the intestine. Conclusion A putative population of gut-derived ex-Trm can be identified in the blood of healthy controls and IBD patients. This population has a distinctive phenotype similar to that of previously described skin-derived ex-Trm. Circulating ex-Trm could link discreet areas of intestinal inflammation in Crohn’s disease and there is a selective loss of the gut ex-Trm population from the blood of these patients. The role of ex-Trm in IBD merits further study.

scholarly journals The gene encoding the interleukin-1 receptor antagonist is differentially expressed in the blood and regulatory T-cells of patients with Crohn’s disease and transcriptionally induced in peripheral blood mononuclear cells upon stimulation with muramyl dipeptide.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Muramyl Dipeptide ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Crohn’s disease, an inflammatory bowel disease (1), is a significant cause of morbidity and economic burden in the United States (2, 3, 4). We performed differential gene expression analyses and identified the interleukin-1 (IL-1) receptor antagonist, IL1RN (5, 6), as among the genes most differentially expressed in the blood and regulatory T-cells of patients with Crohn’s disease using published (7) and public datasets (8). Further analysis of published microarray data (9) revealed that IL1RN was transcriptionally induced upon stimulation of peripheral blood mononuclear cells (PBMC) with muramyl dipeptide, the ligand for the gene product of the Crohn’s disease susceptibility locus NOD2. Interestingly, IL-1RN was expressed at significantly lower quantities in the Treg of patients with Crohn’s disease than in the Treg of non-affected control subjects. This is the first report of differential expression of IL1RN in patients with Crohn’s disease.

scholarly journals Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C

2022 ◽  
Vol 7 ◽  
pp. 11
Author(s):  
Isabelle Williams ◽  
Sumeet Pandey ◽  
Wolfram Haller ◽  
Hein Q. Huynh ◽  
Alicia Chan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Disease Type ◽  
Peripheral Blood Mononuclear ◽  
Niemann Pick Disease ◽  
Blood Mononuclear Cells ◽  
Niemann Pick ◽  
Pick Disease

Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli. Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.

Mo1748 DNA Methylation Profiles of CD4+ Effector Memory T-Cells Show Distinct Differences Between Crohn's Disease and Ulcerative Colitis

2015 ◽  
Vol 148 (4) ◽  
pp. S-701
Author(s):  
Katsunori Matsushita ◽  
Yoichi Kakuta ◽  
Yoshitaka Kinouchi ◽  
Kenichi Negoro ◽  
Katsuya Endo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dna Methylation ◽  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells

Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Physiological Basis ◽  
Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

scholarly journals Lipopolysaccharide and silica-stimulated mononuclear cell prostaglandin production in ulcerative colitis

2000 ◽  
Vol 9 (3-4) ◽  
pp. 189-191
Author(s):  
Neville A. Punchard ◽  
John Cason ◽  
Jonathan Mullins ◽  
Chaman Chander ◽  
Richard P. H. Thompson
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Mononuclear Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Prostaglandin Production ◽  
Blood Mononuclear Cells

Basal, lipopolysaccharide (LPS) and silica-stimulated prostaglandin (PG) production were compared between peripheral blood mononuclear cells (PBMNC) from UC patients and healthy subjects (HS). Basal and LPS-stimulated PBMNC PGI2, but not PGE2, production was greater in UC. LPS stimulated both PGE2and PGI2by PBMNC from HS and UC patients. Silica stimulated production of both PGs by cells from HS but only PGE2by cells from UC patients. The differences in responses to silica and LPS may result from differences in activation of NFκB or, alternatively, prior sensitisation to one of these agents. That PBMNC PGE2production is not increased in UC, as it is in Crohn’s disease, suggests that there are differences in PBMNC behaviour between these two diseases.

scholarly journals Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

2021 ◽  
Vol 10 (17) ◽  
pp. 3822
Author(s):  
Trung T. Vu ◽  
Hanako Koguchi-Yoshioka ◽  
Rei Watanabe
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Adaptive Immune Response ◽  
Psoriatic Skin ◽  
Peripheral Tissues ◽  
Potential Index ◽  
Circulating T Cells ◽  
Chronic Skin ◽  
Resident Memory T Cells

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

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