BackgroundBenign　Lymphoepithelial　Lesion　(BLEL)　is　a　rare　disease　observed　in　the　adult　population.　Despite　the　growing　numbers　of　people　suffering　from　BLEL,　the　etiology　and　mechanisms　underlying　its　pathogenesis　remain　unknown.MethodsIn　the　present　study,　we　used　gene　and　cytokines　expression　profiling,　western　blot　and　immunohistochemistry　to　get　further　insight　into　the　cellular　and　molecular　mechanisms　involved　in　the　pathogenesis　of　BLEL　of　the　lacrimal　gland.ResultsThe　results　showed　that　Macrophage　Migration　Inhibitory　Factor　(MIF)　was　the　most　highly　expressed　cytokine　in　BLEL,　and　its　expression　positively　correlated　with　the　expression　of　Th2　and　Th17　cells　cytokines.　MIF　was　found　to　regulate　biological　functions　and　pathways　involved　in　BLEL　pathogenesis,　such　as　proliferation,　resistance　to　apoptosis,　MAPK　and　PI3K/Akt　pathways.　We　also　found　that　MIF　promotes　fibrosis　in　BLEL　by　inducing　BLEL　fibroblast　differentiation　into　myofibroblasts　as　well　as　the　synthesis　and　the　deposit　of　extracellular　matrix　in　BLEL　tissues.ConclusionsOur　findings　demonstrate　the　contribution　of　MIF　to　the　pathogenesis　of　BLEL　of　the　lacrimal　gland　and　suggested　MIF　as　a　promising　therapeutic　target　for　its　treatment.