Tertiary Lymphoid Organs at the Center Stage of Skin's Humoral Immunity

The skin is the outermost organ that serves as the host's live, microbiota-inhabited physical border, evolved to cope with continuous confrontation by a wide variety of environmental elements. This dynamic borderline is prone to injury and damage. Therefore, to deliver on the critical demands for protection, skin is tightly associated with innate and adaptive defense mechanisms that ensure homeostatic tissue barrier integrity. We recently described the skin's ability to form its own autonomous and protective immune response independently of known professional organs. Cutaneous immunocompetence was achieved through the formation of dermal tertiary lymphoid organs (TLOs) that provide protective humoral activity similar to the classical germinal center reaction in the lymph node. This response was mediated by cutaneous microbiota uncoupled from inflammatory signals and positioned within the healthy skin. Our findings illustrate the power of non-inflammatory host-microbiota interaction and open a door for reevaluation of topical disease development and progression. A detailed understanding of highly coordinated tissue-specific determinants that facilitate local antibody response may provide innovative solutions in skin health care and therapies. In this review, I elaborate on our findings and argue for TLO's importance in the host's immune arsenal, which is at the very center of skin's humoral immunity.