Significance of MAIT Cells in Inflammatory Bowel Disease

Inflammatory Bowel Diseases Clinical Trial

Official title:

Significance and Biological Importance of Mucosal Associated Invariant T Cells in Inflammatory Bowel Disease Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05598346
• Other study ID #: MAIT cells in In IBD
• Status: Not yet recruiting
• Start date: March 1, 2023
• Est. completion date: April 2024

Study information

• Verified date: November 2022
• Source: Assiut University
• Contact: AL- shimaa mohamed salahidden
• Phone: 01010328330
• Email: shoshomylife86[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To examine the level and function of MAIT cells in IBD patients, and to compare it with disease activity.

Description:

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of unknown origin. IBD has become a global disease with increasing incidence in newly industrialized and westernized countries. Genetic and environmental factors with inadequate host immune response to gut flora appear to play important roles in the pathogenesis of IBD. Adaptive immune response has been classically considered to play a major role in IBD pathogenesis .

Infiltrating lymphocytes including T helper (Th) 1 cells and Th17 cells can lead to the development of intestinal lesions . However, recent evidences suggest that innate immune response is equally important in inducing gut inflammation . Altered epithelial barrier function and aberrant innate immune responses contribute to intestinal inflammation in IBD patients.

Mucosal-associated invariant T (MAIT) cells are innate lymphocytes that express a conserved invariant Tcell receptor (TCR) Vα7.2-Jα33 chain paired with a limited set of Vβ chains. Using distinct pairs of TCR chains, MAIT cells can recognize bacteria-derived riboflavin (vitamin B2) metabolites presented by MHC(major histocompatibility complex) class 1b-like related protein (MR1).

Upon MR1-dependent recognition of antigens, MAIT cells are activated to rapidly release Th1/Th17 proinflammatory cytokines (i.e., interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-17 and cytotoxic molecules (i.e.,granzyme and perforin) to kill infected host cells.

MAIT cells are abundant in peripheral blood where they where they express gut-homing chemokine receptors such as CCR6(chemokine receptor type 6) and CCR9(chemokine receptor type9). They are also abundant in intestinal mucosa where they likely confront normal flora or pathogenic bacteria producing bacterial ligands.

Given tissue- homing properties and rapid production of proinflammatory cytokines, MAIT cells may play an important role in infectious diseases and autoimmune disorders.

Results from experiment with transfer of MAIT cells to TNBS(trinitrobenzene sulfonic acid)-induced IBD murine models suggest that MAIT cells might play a protective role in TNBS-induced intestinal inflammation . In addition, previous studies have reported MAIT cell dysfunction in IBD patients. However, the role of MAIT cells in IBD patients remains unclear.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: April 2024
• Est. primary completion date: March 2024
• Gender: All
• Age group: 15 Years to 50 Years

Eligibility

Inclusion Criteria:

• Patients with active IBD according to clinical scores with the following:

1. Recently discovered.

2. Average age (15-50).

Exclusion Criteria:

• Patient with history of any of the following ;

1. History of respiratory disorders such as chronic obstructive diseases, pulmonary disease or pulmonary embolism.

2. Other Autoimmune diseases, infectious diseases.

3. Recent surgery, malignancies, left ventricular dysfunction, use of immunosuppressive drugs.

4. Chronic liver, renal, and endocrine diseases.

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (26)

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Grimaldi D, Le Bourhis L, Sauneuf B, Dechartres A, Rousseau C, Ouaaz F, Milder M, Louis D, Chiche JD, Mira JP, Lantz O, Pène F. Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections. Intensive Care — View Citation

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Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, Lévy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O. Antimicrobial activity of mucosal-associated invariant T cells. Nat Im — View Citation

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Ruijing X, Mengjun W, Xiaoling Z, Shu P, Mei W, Yingcheng Z, Yuling H, Jinquan T. Ja33+ MAIT cells play a protective role in TNBS induced intestinal inflammation. Hepatogastroenterology. 2012 May;59(115):762-7. doi: 10.5754/hge11432. — View Citation

Serriari NE, Eoche M, Lamotte L, Lion J, Fumery M, Marcelo P, Chatelain D, Barre A, Nguyen-Khac E, Lantz O, Dupas JL, Treiner E. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol. 2014 May;17 — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of MAIT cells level in IBD,Compare its level with disease activity	Monoclonal Antibodies by flow cytometry used for detection of MAIT cells in IBD patients	Baseline