A new study is published in the Journal of Experimental Medicine by the Molecular Immunology lab. This study characterizes the FCRL3 receptor as an immunoregulatory molecule that modulates human T cell responses.
The lab of Silvia Monticelli has characterized a receptor that helps keeping immune cells in check. The study, published in the Journal of Experimental Medicine, reveals that the FCRL3 molecule contributes to regulating the activity of human T cells, immune cells crucial for fighting infections but also, in some cases, responsible for driving autoimmune pathologies.
Genetic variants in the FCRL3 gene have been linked to autoimmune diseases such as multiple sclerosis, but the role of the FCRL3 receptor in immune regulation remained only partially understood. The team found that T cells expressing FCRL3 are less prone to activation and show features of specialized “cytotoxic” cells that can kill infected or damaged cells. Moreover, FCRL3 expression was sufficient to limit the activation of these immune cells, potentially contributing to prevent excessive immune responses.
This study was led by co-first authors Niccolò Bianchi, Elena Foli and Mehrpouya Mostanfar, and was made possible thanks to outstanding collaborations within the IRB and with the European Oncology Institute in Milan.
Niccolò says: “The link between FCRL3 and autoimmune diseases was previously known, but studying it has been difficult due to the lack of suitable models. Our work shows how important it is to understand basic cell biology to uncover the connections between molecules and disease.”
This work was supported by an SNSF Excellence Grant. Merhpouya Mostanfar is in part supported by the Ceresio Foundation.
FCRL3 is an immunoregulatory receptor that restrains the activation of human memory T lymphocytes.
Bianchi, N., E. Foli, M. Mostanfar, R. Marzi, M. C. Spinella, S. Polletti, M. Pecoraro, A. Cassotta, R. Thakur, D. Jarrossay, F. Sallusto, G. Natoli and S. Monticelli
J Exp Med. (2026) 223:
