Asset Publisher

Proteins that protect against joint inflammation identified

Proteins that protect against joint inflammation identified

"Endogenous proteins that play a vital part in allergies and parasitic infection can prevent the immune system from wrongly attacking the body and causing inflamed joints, a study by CMM researchers published in the scientific journal PNAS reports. The researchers hope that the results will give rise to new drugs for rheumatoid arthritis.

From left to right: Zsolt Kasza, Sudeepta Kumar Panda, Long Jiang, Fredrik Wermeling, Sanjay Boddul, Yunbing Shen and Vaishnavi Iyer 

In protecting us against infections, our immune systems are vital to our survival. Unfortunately, immune cells can sometimes wrongly attack the body, resulting in what are called autoimmune diseases. These diseases are often serious and affect some five per cent of the population. One example is rheumatoid arthritis, in which the patient’s immune system attacks the joints, causing inflammation and pain. If scientists are to develop better treatments for such patients, they need to understand in detail how immune cells are regulated.

Can prevent autoimmune attacks

Researchers at CMM have now discovered that certain proteins called IL-4 and IL-13 can play an important part in preventing autoimmune attacks. The proteins, which are secreted by immune cells in the presence of allergens or parasitic infections, influence the behaviour of a specific type of immune cell called a neutrophil. Neutrophils are commonly the most abundant immune cells found in the actively inflamed joints of patients with rheumatoid arthritis. They are particularly virulent against tissue since they can secrete various fairly non-specific tissue irritants.

Previous research has shown that IL-4 and IL-13 can affect arthritis in experimental models, but exactly how they do so has remained a mystery. The results of this latest study show that these proteins prevent neutrophils from migrating into the inflamed joint. The presence of IL-4 or IL-13 also stimulates an increase in neutrophil surface receptors which have an inhibiting effect on joint inflammation.

“We will continue to study these mechanisms and hope that our work can contribute to the development of treatments for rheumatoid arthritis,” says principal investigator Fredrik Wermeling, assistant professor at the Department of Medicine, Karolinska Institutet (Solna).

Used the CRISPR method

For their study, the researchers used the CRISPR method to modify selected immune-cell genes in order to understand how they affect cell behaviour. The use of the bacterial CRISPR system as a research method is one of the most significant scientific advances of the past decade.

“The results we obtained using CRISPR were key to quickly understanding how the system under study is regulated,” says Dr Wermeling. “I have high hopes that the experimental use of CRISPR will be hugely important to our understanding of how immune-cell behaviour is regulated, and that this can guide us in the development of new efficacious drugs.”

 

Please read more at the Karolinska Institute here

 

Publication

 IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints. Sudeepta Kumar Panda, Gustaf Wigerblad, Long Jiang, Yanek Jiménez-Andrade, Vaishnavi Srinivasan Iyer, Yunbing Shen, Sanjaykumar V. Boddul, André Ortlieb Guerreiro-Cacais, Bruno Raposo, Zsolt Kasza och Fredrik Wermeling. PNAS, online 20 January 2020, doi: 10.1073/pnas.1914186117.

NEWS

Ning Xu Landén 2020 year’s winner of the LEO Foundation Award

Ning Xu Landén 2020 year’s winner of the LEO Foundation Award Associate Professor Ning Xu Landén, Group Leader at CMM is the winner of this year’s LEO Foundation Award in Region EMEA...

Nils Landegren receives ERC Starting Grant for studying sex differences in the human immune system

Nils Landegren receives ERC Starting Grant for studying sex differences in the human immune system Photo: Hans Ericksson, SSMF Nils Landegren , Researcher at CMM, has been awarded...

Verification project of SARS-CoV-2 antibody tests receives funding from Swelife

Verification project of SARS-CoV-2 antibody tests receives funding from Swelife Photo: Mattias Bronge, Karolinska Institutet A validation project of new SARS-CoV-2 antibody tests,...

Grant to Qiaolin Deng for the single-cell technology core at CMM

Grant to Qiaolin Deng for the single-cell technology core at CMM Qiaolin Deng, private photo We congratulate Associate Professor and CMM Team Leader Qiaolin Deng who received a SFO...

Identification of key gene for improvement of multiple sclerosis treatments

Identification of key gene for improvement of multiple sclerosis treatments Karl Carlström and Fredirk Piehl. Photo: Stefan Zimmermann   CMM researcher Karl Carlström and...

Sweden’s innovation agency Vinnova extends the funding of Genomic Medicine Sweden with additional SEK 36 million

Sweden’s innovation agency Vinnova extends the funding of Genomic Medicine Sweden with additional SEK 36 million Sweden’s innovation agency Vinnova extends the funding of the national...

The Swedish Heart-Lung Foundation major grant 2020 goes to Marie Wahren-Herlenius

The Swedish Heart-Lung Foundation major grant 2020 goes to Marie Wahren-Herlenius Professor Marie Wahren-Herlenius, Group Leader at CMM, has received the biggest yearly grant in Sweden...

Simple blood test may help predict MS progression, study finds

Simple blood test may help predict MS progression, study finds Photo: Ali Manouchehrinia   A study led by the CMM researchers Ali Manouchehrinia (first...

Experimental study finds new substances with higher specificity and therapeutic potential in multiple sclerosis

Experimental study finds new substances with higher specificity and therapeutic potential in multiple sclerosis   Karl Carlström, photo Stefan Zimmerman   Karl...

Early exposure to cannabis boosts young brains' sensitivity to cocaine, rodent study shows

Early exposure to cannabis boosts young brains' sensitivity to cocaine, rodent study shows A study made by Philippe Melas from Karolinska Institutet together with colleagues at Columbia...