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Pavel Hanč Lab
Peripheral Neuroimmunology
Pavel Hanč Lab
Peripheral Neuroimmunology
Pain has been recognized as a cardinal sign of inflammation ever since the time of the Roman physician Celsus. Yet, only in the past decade has it become clear that such neuroimmune communication is bidirectional: it’s not just that inflammation begets pain, but pain and, specifically, nociceptors – the neurons that mediate the sensation – can also shape immunity. Indeed, nociceptors, in a context-dependent manner, promote, skew, or inhibit immune responses across various conditions ranging from allergies to cancer, from infection to tissue repair.
The focus of the Peripheral Neuroimmunology Lab is to explore the molecular mechanisms underlying the neuroimmune communication between nociceptors and the immune system, and to understand the logic that dictates the ultimate outcome of such interactions.
The lab is currently focused on three non-overlapping, conceptually related areas of research:
- Communication between nociceptors and dendritic cells
- Role of nociceptor : monocyte dialog in tumorigenesis
- Discovery of novel neuroimmune interactions and their molecular mechanisms
1) Dendritic cells (DCs) are myeloid leukocytes essential for the initiation and regulation of immune responses. In previous work, we have shown that nociceptors use at least three molecularly distinct, context-dependent mechanisms, including direct electrical coupling, the neuropeptide CGRP, and the chemokine CCL2, to fine-tune DC functions. We are currently interested in further elucidating how these communications shape DC-driven immunity in various biological contexts and testing whether they could represent clinically tractable targets.
2) We have recently found that nociceptors can promote tumor growth in a mouse model of urinary bladder cancer by inducing an anti-inflammatory phenotype in tumor-infiltrating monocytes, which, in turn, prevents T-cell-mediated tumor eradication. We are now interested in identifying the mechanism(s) of nociceptor: monocyte communication and testing if their targeting could be therapeutically beneficial. In a separate set of studies, we will test the involvement of nociceptors in the process of metastasis as well as in other tumor models.
3) While nociceptive neuropeptides, including the calcitonin gene-related peptide (CGRP), substance P, and others, have received much attention for their ability to affect immune cell functions, they are not the only mechanisms through which nociceptors and the immune system communicate. However, the inherent complexity of neuroimmune interactions complicates systematic dissection of the underlying molecular mechanisms. Thus, we have recently developed an ex vivo co-culture system that enables the exploration of neuroimmune interactions under defined conditions. We are now interested in further developing and utilizing this approach to assess which types of immune cells can receive communication signals from nociceptors, understand the relevant biological contexts, and uncover the underlying molecular mechanisms.