**5. Implication of CCL17, CCL22 and CCR4 in other diseases**

In addition to AD, enhanced expression of CCL17 and CCL22, as well as elevated frequencies of CCR4+ T cells have been observed in asthma (Panina-Bordignon et al., 2001; Vijayanand et al., 2010) and rhinitis (Takeuchi et al., 2005; Terada et al., 2001), the two other forms of atopic diseases. In the case of asthma the pathogenic role of the CCL17/CCL22- CCR4 axis is still controversial (Pease, 2006), as some reports demonstrate efficient improvement of disease symptoms after CCR4 or CCL17 blockade (Kawasaki et al., 2001; Perros et al., 2009; Vijayanand et al., 2010), whereas others do not ( Chvatchko et al., 2000; Conroy et al., 2003). As already mentioned above, enhanced expression of CCL17 and CCL22 has also been observed in allergic contact dermatitis (Bäumer et al., 2004; Goebeler et al., 2001; Kamsteeg et al., 2010; Martín et al., 2002), and contact hypersensitivity responses were significantly inhibited in CCL17-deficient mice (Alferink et al., 2003). Regarding nonallergic diseases, CCL17 has recently been shown to enhance the formation of artherosclerotic lesions in mice by inhibition of Treg cell expansion (Weber et al., 2011). Furthermore, deficiency in CCL17 or CCR4 prolongs graft survival in mouse models of cardiac allograft rejection (Alferink et al., 2003; Hüser et al., 2005).

As CCL17 expression is strongly upregulated in response to TLR stimulation (Lieberam & Förster, 1999; Alferink et al., 2003), it is possible that this chemokine is also involved in the defence against microbial infections. After cutaneous infection with the murine filaria *Litomosoides sigmodontis*, CCL17 was shown to control filarial worm load as a consequence of reduced mast cell dependent larval entry (Specht et al., 2011). In contrast, blockade of CCL17 but not CCL22 enhanced protection from murine pulmonary aspergillosis, and CCR4-deficient mice were similarly protected (Carpenter & Hogaboam, 2005). CCL17 production induced by NKT cell activation licensed splenic DC for efficient crosspresentation of OVA and stimulation of CTL responses (Semmling et al., 2010). Thus, CCL17 may also be involved in the defence against viral infections, although this has not been directly assessed so far.

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