CCL22 was initially cloned from human activated macrophages by random sequencing of cDNA clones. CCL22 was described originally as a constitutively produced, thymus-specific chemokine engaged in the recruitment of T cells. CCL22 and CCL17 bind to CCR4, and both chemokines share similar in vivo expression patterns and are closely linked on human chromosome 16; nevertheless, they are only 37% identical at the amino acid level. CCL22 has been associated to different diseases such as allergen-induced lung inflammation, atopic dermatitis, and lymphoma. Also, high levels of CCL22 have been detected in the CNS in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In addition, CCR4+ T cells have been linked to endotoxic shock, rheumatoid arthritis, T cell lymphoma, and autoimmune diabetes. Recruitment of Tregs to human cancers producing CCL22 suppresses tumor-specific T cell immunity and contributes to tumor growth. In the context of central nervous system, CCR4 is expressed in astrocytes, microglia, and in hippocampal neurons. Most recently, CCR4 and CCL22 have been detected in the anterior hypothalamus/preoptic area, a key region involved in thermogenesis. In this sense, it has been described that CCL22 is a prostaglandin-dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.