AUTHOR=Jain Shweta , Stock Ariel , Macian Fernando , Putterman Chaim 

TITLE=A Distinct T Follicular Helper Cell Subset Infiltrates the Brain in Murine Neuropsychiatric Lupus

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00487

DOI=10.3389/fimmu.2018.00487

ISSN=1664-3224

ABSTRACT=Neuropsychiatric symptoms in systemic lupus erythematosus are not uncommon, yet the mechanisms underlying disease initiation and progression in the brain are incompletely understood. Although the role of T cells in other lupus target organs such as the kidney is well defined, which T cells contribute to the pathogenesis of neuropsychiatric systemic lupus erythematosus is not known. The present study was aimed at characterizing the CD4 T cell populations that are present in the choroid plexus of MRL/MpJ-faslpr mice, the primary site of brain infiltration in this classic lupus mouse model which exhibits a prominent neurobehavioral phenotype. 

T cells infiltrating the choroid plexus of MRL/MpJ-faslpr mice were characterized and subset identification was done by multiparameter flow cytometry. We found that the infiltrating CD4 T cells are activated and have an effector function. Importantly, CD4 T cells have a T follicular helper cell (TFH) like phenotype, as evidenced by their surface markers and signature cytokine, IL-21. In addition, CD4 TFH cells also secrete significant levels of IFN-γ and express Bcl-6, thereby conforming to a pathogenic T helper population that can drive the disease progression. Interestingly, the regulatory axis comprising CD4 T regulatory cells is diminished. These results imply that accumulation of pathogenic CD4 T follicular helper cells in the brain of MRL/MpJ-faslpr mice contributes to the neuropsychiatric manifestations of systemic lupus erythematosus, and suggest this T cell subset as a novel therapeutic candidate.