IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease."

It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to an analysis of up to 500 patients with IBD and 100 controls, we report that key transcripts of the IL-7 receptor (IL-7R) pathway are accumulated in inflamed colon tissues of severe CD and UC patients not responding to either immunosuppressive/corticosteroid, anti-TNF, or anti-α4β7 therapies. High expression of both IL7R and IL-7R signaling signature in the colon before treatment is strongly associated with nonresponsiveness to anti-TNF therapy. While in mice IL-7 is known to play a role in systemic inflammation, we found that in humans IL-7 also controlled α4β7 integrin expression and imprinted gut-homing specificity on T cells. IL-7R blockade reduced human T cell homing to the gut and colonic inflammation in vivo in humanized mouse models, and altered effector T cells in colon explants from UC patients grown ex vivo. Our findings show that failure of current treatments for CD and UC is strongly associated with an overexpressed IL-7R signaling pathway and point to IL-7R as a relevant therapeutic target and potential biomarker to fill an unmet need in clinical IBD detection and treatment.


Journal Details

This article was published in the following journal.

Name: The Journal of clinical investigation
ISSN: 1558-8238


DeepDyve research library

PubMed Articles [30395 Associated PubMed Articles listed on BioPortfolio]

Management of Biological Therapy Before Elective Inflammatory Bowel Disease Surgeries.

Increasing uptake of biologic therapy has contributed to declining surgical rates for inflammatory bowel disease (IBD). However, a significant number of patients on biologic therapy will go on to requ...

ZNF133 Is Associated with Infliximab Responsiveness in Patients with Inflammatory Bowel Diseases.

Infliximab has been widely prescribed for treating inflammatory bowel disease (IBD). However, the response rates to infliximab differ among patients. Therefore, we aimed to identify the genetic and cl...

Lack of Vitamin D Receptor Leads to Hyperfunction of Claudin-2 in Intestinal Inflammatory Responses.

Vitamin D3 and vitamin D receptor (VDR) are involved in the pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin-2 is a junction protein that mediates paracellular water t...

Anti-Tumor Necrosis Factor Therapy for Inflammatory Bowel Diseases Do Not Impact Serious Infections After Arthroplasty.

There is a paucity of data on the safety of joint replacement surgery in patients with inflammatory bowel disease (IBD), including those on tumor necrosis factor-alpha inhibitors (anti-TNF). We explor...

Acute Colitis Drives Tolerance by Persistently Altering the Epithelial Barrier and Innate and Adaptive Immunity.

Inflammatory bowel disease (IBD) has a remitting and relapsing disease course; however, relatively little is understood regarding how inflammatory damage in acute colitis influences the microbiota, ep...

Clinical Trials [16674 Associated Clinical Trials listed on BioPortfolio]

Joint Pain Occurring During Anti-TNF Therapy in Chronic Inflammatory Bowel Disease

IBD (inflammatory bowel disease) are associated with various types of joint manifestations, especially inflammatory. Patients with IBD treated with anti-TNF commonly report joint symptoms,...

Anti CT-P13 Antibody in Moderate to Severe Inflammatory Bowel Disease

The purpose of this study is to evaluate the development of anti-drug antibody to biosimilar CT-P13 and to assess the change of drug concentration for 1 year in patients with moderately to...

Decisional Influences and Inflammatory Bowel Disease (IBD) Patients' Medication Use

The primary purpose of this study is to pilot test an instrument that the investigators will develop to assess decision influences on inflammatory bowel disease patients' medication adhere...

Osteoprotegerin and sRANKL as Marker in Early Diagnosis of Inflammatory Bowel Disease

The inflammatory bowel diseases represent a heterogeneous group of chronic , relapsing- inflammatory disorders of the gastrointestinal tract. Crohn's disease and ulcerative colitis are the...

Predictors of Mucosal Healing in Inflammatory Bowel Disease (IBD) Patients Treated With Anti-TNF

The aim of this study is to prospectively identify, at diagnosis of the disease, factors predictive of mucosal healing in patients with inflammatory bowel disease treated with anti-TNF.

Medical and Biotech [MESH] Definitions

An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)

A species of Faecalbacterium, previously classified in the FUSOBACTERIUM genus, that is a major constituent of the GUT MICROBIOTA in healthy humans. It has anti-inflammatory activity and reduced numbers of this species occur in patients with INFLAMMATORY BOWEL DISEASES such as CROHN DISEASE.

Anti-inflammatory agents that are not steroids. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Certain NSAIDs also may inhibit lipoxygenase enzymes or TYPE C PHOSPHOLIPASES or may modulate T-cell function. (AMA Drug Evaluations Annual, 1994, p 1814-5)

A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.

An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of ASTHMA.

Quick Search


DeepDyve research library

Relevant Topic

Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...

Searches Linking to this Article