ORIGINAL RESEARCH article
Front. Immunol.
Sec. Antigen Presenting Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1611812
Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals
Provisionally accepted
- 1Thomas Jefferson University, Philadelphia, Pennsylvania, United States
- 2Baylor Scott & White Research Institute (BSWRI), Dallas, Texas, United States
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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 canonical 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 system's role in maintaining tolerance or developing autoimmunity under non-inflammatory conditions.
Keywords: Langerhans cell, Steady - state, Adaptive Immunity, dendritic cell, TFH, B cell
Received: 14 Apr 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Bouteau, Qin, Zurawski, Zurawski and Igyártó. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Botond Z Igyártó, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, United States
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