CCBIO Special Seminar – Michael Rogers
Michael Rogers, Harvard Medical School and the Vascular Biology Program, Boston Children's Hospital, will give a talk on intriguing discoveries recently made in his laboratory about interactions among lesions, nerves, and immune cells in endometriosis. Join us also for the informal pizza get-together in the hall following the talk!
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Welcome to a CCBIO Special Seminar on the topic metastasis without a tumor.
Speaker: Michael Rogers, Harvard Medical School and the Vascular Biology Program, Boston Children's Hospital
Title: “Neuro-immune communication in endometriosis, a novel therapeutic target?”
Chair: Agnete Engelsen
When: Thursday March 23 at 14.30-15.45
Place: Auditorium 4, BBB, Bergen
Join us also for the informal pizza get-together in the hall following the talk!
Abstract: Endometriosis is a painful and debilitating inflammatory disease that affects approximately 10% of reproductive-age women. Treatment options are currently limited to NSAIDs, hormones, and surgery. For ~30% of patients, none of these options are effective and for many, symptom relief is only temporary. Because neuroimmune communication plays a role in several inflammatory conditions, we sought evidence for a role for neuroimmune communication in endometriosis-associated pain and lesion growth.
To that end, we leveraged our mouse model of endometriosis-associated pain. We found that:
- Mouse and human lesions are highly innervated by peptidergic nociceptors. In lesion-bearing mice, dorsal root ganglia (DRGs) showed activation of peptidergic nociceptors.
- Calcium imaging of mouse DRG neurons showed that mouse endometriosis lesions directly activate nociceptors. Lesion-secreted VEGF and PLGF induce neuropeptide release by cultured DRG neurons.
- Targeted ablation of TRPV1+ nociceptors by genetic (TRPV1-cre/DTA) or chemical (RTX) means reduced not only mechanical and spontaneous pain, but also lesion size, suggesting that neuropeptide release contributes to lesion maintenance and/or growth.
- Blocking TRPV1+ nociceptor signaling reduced neuropeptide release in vitro and mechanical and spontaneous pain, and lesion size in mice.
- RTX-treatment reduced F4/80+Ly6C+ cells both in the peritoneal cavity (PerC) and lesions. In co-culture, CGRP stimulated mouse PerC macrophages to release soluble factors that stimulate endometriosis epithelial cell growth. CGRP also impaired macrophage efferocytosis. Depleting resident macrophages with clodronate reduced endometriosis lesion size.
- Blocking CGRP-RAMP1 signaling with 4 different drugs reduced pain and lesion size on our mouse model.
We conclude that neuroimmune communication mediates lesion growth and pain in our endometriosis model. This implies that blocking neuroimmune communication may be effective in treating endometriosis. A salient example of such an approach would be CGRP pathway antagonists currently used for migraine.