Biology subjects

Hanc, P.

Publications and source records attributed to Hanc, P..

3 recordsLinked to original sources

bioRxiv2026

Monocyte reprogramming by nociceptors impedes T cell-mediated tumor immunity

Nociceptors - peripheral nervous system neurons that trigger the sensation of pain or itch in response to noxious stimuli - can communicate with leukocytes and modulate immune responses in a context-dependent manner1,2. Here, we demonstrate that nociceptors rapidly induce monocytes to adopt an immunosuppressive phenotype, reminiscent of myeloid-derived suppressor cells (MDSCs), which have been linked to impaired anti-tumor immunity. MDSCs are abundant in human bladder cancer, a malignancy where survival is negatively correlated with expression of pro-neurogenic cytokines. Accordingly, in an orthotopic mouse model of urinary bladder carcinoma, incipient tumors promoted dense innervation by nociceptors and infiltration by monocytes that differentiated rapidly into MDSCs. Nociceptors did not affect the development of tumor-specific T cells in draining lymph nodes, but they were essential during the early stages of tumor formation to establish an immunosuppressive tumor microenvironment. Ablation or chemogenetic inhibition of nociceptors prevented the formation of immunosuppressive MDSCs and markedly increased the rate of bladder tumor rejection by T cells. Conversely, monocyte depletion in nociceptor-sufficient mice enabled tumor rejection. Collectively, these findings demonstrate that urothelial tumors co-opt an immunosuppressive neuro-immune axis to evade anti-tumor immunity and identify nociceptors as potential targets for bladder cancer treatment.

immunology↗

bioRxiv2025

Major histocompatibility complex class II-expressing bone marrow megakaryocytes activate CD4+ T cells and induce regulatory T cell fate

While professional antigen-presenting cells drive adaptive immunity, atypical cell types can fulfill this role in the bone marrow. Megakaryocytes (MKs) are canonically recognized for platelet production, but recent studies indicate functional heterogeneity and immune potential. We found that ~20% of bone marrow MKs express Major Histocompatibility Complex (MHC) II and co-stimulatory receptors CD80, CD86, CD40, and CD83. These MKs process and present antigen to activate T cells ex vivo in an MHC II-dependent manner. MK/T cell interactions induced TGF-{beta}1 secretion and promoted induced Treg differentiation. Prior stimulation of MKs with LPS or Poly I:C was associated with modest Th1-associated CD4+ T cell responses, including IFN-{gamma} and TNF- production, without robust Th17 differentiation. Immunopeptidomics of the murine MK MHC II receptor confirmed occupancy by exogenous peptides, suggesting in vivo functionality. Using a murine model with MK-targeted deletion of MHC II (Pf4-MHC{Delta}/{Delta}), we observed altered TLR signaling and reduced bone marrow TGF-{beta}1. Together, these findings identify MHC II+ MKs as noncanonical antigen-presenting cells with the potential to modulate CD4 T cell responses as part of the immune regulation of the bone marrow niche.

immunology↗

bioRxiv2024

Constitutive immune surveillance of nasal mucosa by three neutrophil subsets with distinct origin, phenotype, and function

The nasal mucosa (NM) has several critical functions, including as a chemosensory organ, as a filter and conditioning surface of inhaled air for the lower airways, and as a first line of defense against airborne infections. Owing to its constant exposure to ever-changing environments, the NM is arguably the most frequently infected tissue in mammals. Consequently, vertebrates harbor an intricate network of subepithelial immune cells that are dispersed throughout the NM. However, the origin, composition, and function of nasal immune cells and their pathophysiological role are poorly understood. Here, we show that murine steady-state NM harbors a prominent population of extravascular neutrophils (EVN) that are abundant in both conventional and germ-free mice, suggesting that their presence is not driven by microbial stimuli. Nasal EVN can be subdivided into three phenotypically distinct subsets: one population that we have termed nN1 is CD11bint Ly6Gint, while the other two subsets are both CD11bhi Ly6Ghi and distinguishable by the absence (nN2) or presence (nN3) of CD11c and SiglecF. nN1 EVN originate in bone marrow (BM) within osseous structures in the skull. These locally produced neutrophils appear to access the adjacent NM via conduits that connect BM cavities to the submucosal lamina propria. nN2 cells reach the NM via the blood and readily engulf infectious microbes. In the absence of infection, nN2 cells differentiate into the nN3 subset, which does not capture microbes but assumes phenotypic and functional features of antigen-presenting cells, including the capacity to cross-present exogenous antigens to CD8 T cells. These findings indicate that steady-state mammalian NM harbors a unique innate cellular immune environment that is unlike any other barrier tissue.

immunology↗