CD40 expression in uterine tissues: A key regulator of cytokine expressionby fibroblasts

CD40 is a cell surface receptor initially discovered on cells of the hemopo ietic lineage. Its primary role on immune cells is to enhance their activat ion and hence their production of cytokines and immunomodulatory molecules. Recently, CD40 has also been detected on human fibroblasts. An emerging vi ew of the fibroblast is that it is far more than a structural cell, being c apable of intimate interaction with cells of the immune system. In fibrobla sts from several tissues, the engagement of CD40 with its ligand (CD40L) re sulted in the secretion of proinflammatory molecules such as interleukin-6 (IL-6) and IL-8. Currently, there are few data about the presence of the CD 40-CD40L system in female reproductive tissues. This study investigates the expression of CD40 by human endometrium, myometrium, and cenix both in sit u and in tissue explant-derived fibroblasts. CD40 was detected mainly in th e perivascular region of endometrium, myometrium, and cervix. Light stainin g for CD40 was observed in stromal elements. Additionally, the basal epithe lium of cenix expressed CD40. Fibroblastic cells derived from all three sou rces express low levels of CD40, and this is up-regulated with interferon-g amma treatment (500 U/mL; 72 h). When activated with interferon-gamma and C D40L, the fibroblasts secreted increased amounts of IL-6, IL-8, and MCP-1. These data suggest that the CD40-CD40L system may provide a link between th e resident structural cells of these reproductive tissues and the infiltrat ing immune cells or activated platelets that may express CD40L. The possibl e interaction of CD40 with CD40L may be particularly important during event s such as menstruation and cervical ripening, where up-regulation of the pr oinflammatory molecules IL-6 and IL-8 is viewed as critical for these proce sses. In addition, dysregulation of this system may be a contributory facto r to problems such as menstrual dysfunction and preterm labor.