The immune system of a fish has cellular and molecular defense mechanisms that are
substantially retained throughout the evolution of vertebrates. The innate immune system provides
biological processes, such as phagocytosis and mechanical barriers, to implement an efficient defensive
response after exposure to chemical or biological contaminants, pollutants, and contact with
parasites, germs, and pathogens. Club cells (CCs) are widespread in the skin of Ostariophysi. After
a predator attack or exposure to toxins and parasites, these cells can produce alarming substances.
Given their effectiveness against viruses, parasites, and common skin lesions, recent studies have
suggested that CCs are a component of the immune system. This study aims to immunohistochemically
characterize the CCs for the first time in the skin of zebrafish, using mitogen-activated
protein kinase (MAPK) p38, Toll-like receptor (TLR)2, Piscidin1, and inducible nitric oxide synthase
(iNOS) peptides involved in the function of all types of vertebrate immune cells. According to our
analysis, the intermediate layer of the epidermis exhibited rounded, oval, and elongated CCs, with
central acidophilic cytoplasm and a spherical basophilic nucleus, that are positive to the antibodies
tested. Our results may confirm that CCs could be involved in the immune function, increasing our
knowledge of the immune system of teleosts.