GM-CSF production by immune cells in steady state and autoimmune neuroinflammation mapped using fate reporting mice

Gholamreza Azizi¹Javad Rasouli¹Hamed Naziri¹Michael Gonzalez²James Garifallou²Guang-Xian Zhang¹Bogoljub Ciric¹Abdolmahamad Rostami^1*

• ¹Thomas Jefferson University, Philadelphia, United States
• ²Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Introduction: GM-CSF is a pro-inflammatory cytokine that promotes an inflammatory phenotype in myeloid cells. The extent and pattern of GM-CSF expression in immune cells have not been fully elucidated. Our goal was to advance this topic using novel GM-CSF reporter/fate reporter transgenic mice.We tracked ongoing and past GM-CSF expression in various immune cells from multiple organs, in steady-state and autoimmune inflammation of the central nervous system (CNS).The GM-CSF expression patterns varied by cell type and organ, with CD4 + , CD8 + , and CD11b + cells being the main producers. GM-CSF expression was transient and seemingly permanently lost in most cells over time. In a mouse model of CNS autoimmunity, effector memory CD4⁺ T cells were the dominant GM-CSF source in the CNS. A large proportion of CD4 + T cells that expressed GM-CSF also expressed CXCR6, but this chemokine receptor did not play a role in the CNS autoimmunity. Transcriptomic analysis showed notably distinct gene expression profiles between effector memory CD4 + T cells that did and did not express GM-CSF.Discussion: These findings identified distinct GM-CSF cellular sources across organs, highlighting the transient nature of GM-CSF expression and the correlation between its expression and the overall phenotype of effector memory CD4 + T cells.