# Langerhans cells drive Tfh and B cell responses independent of canonical cytokine signals

## TL;DR

Langerhans cells can activate immune responses without needing typical inflammatory signals, changing how we understand immune system regulation.

## Contribution

The study reveals that Langerhans cells drive Tfh and B cell responses without relying on canonical cytokine signals like IL-6 or interferons.

## Key findings

- Langerhans cells induce Tfh and B cell responses without IL-6, type-I interferons, or ICOS-L signaling.
- CD80/CD86-mediated co-stimulation is essential for LC-driven immune responses in steady-state conditions.
- These findings challenge the traditional three-signal model of adaptive immunity.

## 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 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.