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bioRxiv · 10.1101/2025.01.10.632426

Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals

Bouteau, A.·Qin, Z.·Zurawski, S.·Zurawski, G.·Igyarto, B.
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Abstract

Dendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models and in vitro systems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses. We found that LCs drive germinal center Tfh and B cell differentiation and antibody production independently of interleukin-6 (IL-6), type-I interferons, and ICOS ligand (ICOS-L) signaling, which are critical in inflammatory settings. Instead, these responses relied on CD80/CD86-mediated co-stimulation. Our findings challenge the conventional three-signal paradigm by demonstrating that cytokine signaling is dispensable for LC-mediated Tfh and B cell responses in steady-state. These insights provide a framework for understanding homeostatic immunity and the immune systems role in maintaining tolerance or developing autoimmunity under non-inflammatory conditions. SUMMARY STATEMENTLangerhans cells (LCs) drive germinal center Tfh and B cell responses in steady-state conditions independently of IL-6, type-I interferons, and ICOS ligand, challenging the established cytokine-centric model of T cell differentiation.

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Bouteau, A., Qin, Z., Zurawski, S., Zurawski, G., Igyarto, B.. 2025-01-14. Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals. https://doi.org/10.1101/2025.01.10.632426

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