ADAPTIVE SKIN CARE 73
The tolerogen: restoring tolerance in urban skin
Òscar Expósito, Mª Ángeles Monzón, Victoria Vidal, Ana Gallego, Sandra Ruiz, Pau Riera, Daniel Luna, Xinwei Zhao, Maria Mas, Marta Gibert, Laura Cano, Sara Laplana, Tarik Ruiz, Laura Facchini, Raquel Ferreira, Alejandro Guirado - Vytrus Biotech
Urbanisation has fundamentally altered the skin’s operating environment. Contemporary lifestyles expose the skin to a sustained cocktail of indoor and outdoor pollutants (fine particulate matter (PM2.5), volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), and combustion by-products) (Figure 1), which disrupts the skin’s structural integrity and immune homeostasis. Accumulating evidence supports the
role of these environmental aggressors in triggering persistent low-grade inflammation, barrier dysfunction, and immune hyperreactivity, which collectively manifest as the chronic redness, sensitivity, and reactivity increasingly prevalent in urban populations.1-3 The world is becoming increasingly
urbanised, with urban residents typically spending 80-90% of their time indoors,4,5
where pollutant
concentrations can exceed outdoor levels by a factor of two to three, rising to ninefold above outdoor levels during cooking events.6-8 Indoor pollution (heavy metals, pesticides, industrial chemicals, VOCs, and particulate matter) is the unaddressed driver of the sensitive skin epidemic.1,3
Prolonged pollutant exposure appears
to act as a chronic biological stressor by increasing ROS, inflammatory cytokines, and barrier impairment, and PM2.5 has been reported to trigger chronic immune activation and increased skin sensitivity.9,10
The resulting phenotype (urban
sensitive or hyperreactive skin) represents a growing unmet need. Conventional management of sensitive skin
has focused on immediate relief: soothing, calming, blocking, or reducing visible symptoms,11 while 60–70% of global consumers self-identify as having sensitive skin.12
Yet the paradox is
clear: more sensitive skin products on the market correlate with more reactive consumers. These approaches do not target the underlying
immune dysregulation driving the condition, because the root cause is not inflammation; inflammation is the output. Vytrus Biotech introduces a fundamentally different paradigm: immune re-education. Rather than suppressing the signal, the objective is to educate immune cells to stop over-reacting to harmless stimuli.
The role of Langerhans cells: the skin’s immune decision-makers Langerhans cells (LC) are the pivotal decision-
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makers of the skin’s immune response, comprising 3–5% of epidermal cells. In healthy unexposed skin, LC maintain a steady-state tolerogenic phenotype: alert but calm, capable of distinguishing between genuine threats and harmless environmental stimuli.13,14 They operate as a biological switch, capable
of driving either tolerance or inflammation depending on the molecular context of the stimulus they receive (Figure 2). Continuous exposure to indoor pollutants lowers the
ABSTRACT
Urban skin is exposed to a sustained load of indoor and outdoor pollutants that lowers the threshold of the cutaneous immune response, producing the redness, discomfort and reactivity that characterise hyperreactive skin. Conventional sensitive skin actives suppress the inflammatory output rather than correcting the dysregulation that generates it. Toleroxyl™, a recombinant human GM-CSF produced in a plant
biofactory system, is presented here as the first cosmetic tolerogen: an active that re-educates Langerhans cells towards a
tolerogenic phenotype instead of blocking their response. In a reconstructed human epidermis model containing Langerhans cells and challenged with an indoor pollution mixture, the active normalised the immune activation markers CCR7, CD80, CD86 and IL-8 to physiological levels, enhanced the tolerogenic mediators RELB, SOX4 and TGF-β, and restored barrier and junctional proteins. Two randomised, double-blind, placebo-controlled studies in volunteers with dermatologically confirmed hyperreactive skin reproduced these effects in vivo, with redness reduced up to 65.3%,, clinically confirmed erythema improvement, and lower stratum corneum cytokine levels
Figure 1: Sketch of indoor PM2.5 source and exposure October 2026 PERSONAL CARE MAGAZINE
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