Journal Article Ppublish
PubMed: 41091129 DOI: 10.1084/jem.20242474
FCRL3 is an immunoregulatory receptor that restrains the activation of human memory T lymphocytes.
J Exp Med 223(1)
Authors: Niccolò Bianchi, Elena Foli, Mehrpouya Mostanfar, Roberta Marzi, Mara Cetty Spinella, Sara Polletti, Matteo Pecoraro, Antonino Cassotta, Roshan Thakur, David Jarrossay, Federica Sallusto, Gioacchino Natoli, Silvia Monticelli
Affiliations
- Institute for Research in Biomedicine, Università della Svizzera italiana , Bellinzona, Switzerland.
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
- Institute for Microbiology, ETH Zurich , Zurich, Switzerland.
Abstract
Genetic variants in the FCRL3 gene are linked to autoimmune disorders. However, the functional properties of FCRL3-expressing T lymphocytes, and the regulation and functional impact of FCRL3 expression remain understudied. Here, we performed a multiomic and functional analysis of human T lymphocytes expressing FCRL3. FCRL3 expression correlated with reduced capacity of T cells to undergo activation and was accompanied by functional specialization toward a cytotoxic phenotype, resembling cytotoxic CD4+ T lymphocytes and CD8+ effector memory TEMRA cells. FCRL3 expression was induced upon repetitive TCR engagement, and sufficed to attenuate T cell responses, indicating a role as a negative regulator of the activation of differentiated T cell subsets with high cytotoxic capacity. Mechanistically, the cytoplasmic domain of FCRL3 engaged inhibitory molecules, suggesting a direct role in limiting activating signals. Overall, our study establishes FCRL3 as a functional immunoregulatory receptor that restrains the activation of highly specialized human memory T cells.
MeSH
Cells, Lymphocytes, Memory, T-Lymphocytes