Characterizing the genetic factors impacting the immune response in type 1 diabetes

A new study performed has offered better knowledge about how genetic factors tend to impact the immune response of the body in type 1 diabetes.

Image Credit: vchal/Shutterstock.com

Image Credit: vchal/Shutterstock.com

The study has been reported in the eLife journal.

The outcomes offer proof of a direct link present between genetic factors connected with vulnerability to type 1 diabetes and immune functionality. This especially involves immune T cells. Also, they stress 11 genes that can be explored as possible candidates for new treatments.

Type 1 diabetes gets developed when the immune system of the body attacks groups (or islets) of insulin-producing beta cells present in the pancreas. At present, there are more than nine million people who have been diagnosed with type 1 diabetes

However, there is no cure for this condition and hence it is necessary for patients to have regular insulin injections to control the condition. People with few genetic variations are highly vulnerable to type 1 diabetes. However, while earlier studies have determined almost 60 linked changes, it is yet to be known how they impact the condition.

To characterize the body’s immune response in type 1 diabetes, we need to look at both the proportion of immune cells and their production of proteins—cytokines—that stimulate the immune system.”

Xiaojing Chu, Doctorate Student, University Medical Center Groningen

Chu added, “In our study, we explored how genetic factors affect immune cells and their cytokine production in people with type 1 diabetes, as well as the differences between the immune response in patients and a healthy response.”

Chu is a co-first author of the study together with Anna Janssen, a Medical Doctor and PhD Candidate, and Hans Koenen, Assistant Professor, at Radboud University Medical Center, the Netherlands

The scientists gathered blood samples from nearly 243 volunteers of Dutch descent with type 1 diabetes. The age of the patients ranged from 20–84 years. Further, they employed a method known as genetic association analysis on more than 100 cytokine production profiles and over 200 immune cell traits to determine genetic determinants of immune functionality.

The researchers made a comparison of the results to those achieved in a group of almost 500 healthy individuals from earlier studies that characterized the effect of genetic factors on immune responses in such individuals.

Their analyses displayed those genetic variants identifying the susceptibility to type 1 diabetes considerably impact T-cell composition. Particularly, a group of such cells, known as CCR5+ regulatory T cells, was involved actively in type 1 diabetes via an area of the genome known as the constrained coding region.

Furthermore, the team utilized a method known as genome-wide quantitative trait loci (QTL) mapping to examine immune traits. This disclosed 15 genetic “commands” that impact the behavior of immune cells in type 1 diabetes.

Amongst these, 12 have not earlier been reported in healthy people, denoting a disease-specific genetic regulation. Besides, the team determined 11 genes as possible candidates for drug development.

Our findings provide a deeper understanding of the immune mechanisms involved in the development of type 1 diabetes and that affect the general inflammatory response in patients. We hope this work will open up new avenues for the development of much-needed treatments.”

Yang Li, Professor, Computational Biology, Helmholtz Centre for Infection Research

Li is also the Director of the Centre for Individualized Infection Medicine.

Li is a co-senior author of the study together with Cees Tack, Professor in Internal Medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

Source:
Journal reference:

Chu, X., et al. (2022) A genome-wide functional genomics approach uncovers genetic determinants of immune phenotypes in type 1 diabetes. eLife. doi.org/10.7554/eLife.73709

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