Yamanaka K, Clark R, Rich B et al.Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma. Blood 107:2440-2445

Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115, USA.
Blood (Impact Factor: 10.45). 04/2006; 107(6):2440-5. DOI: 10.1182/blood-2005-03-1139
Source: PubMed


Cutaneous T-cell lymphomas (CTCLs) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL.

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    • "Previous evidences had suggested the important role of IL-7 in the pathogenesis and progression of lymphomas [3, 15]. In breast cancer cell lines, IL-7 could induce the growth of cells, while this effect involved PI3K and Jak3 [16]. "
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    • "However, cytokines that signal through receptors containing the common cytokine receptor g chain (g c ) have been shown to be vital for the ex vivo survival and proliferation of the malignant T cells. Because some of these g c cytokines are present in CTCL patients, it has been suggested that they have an important role in the pathogenesis (Dobbeling et al., 1998; Leroy et al., 2001; Yamanaka et al., 2006b; Marzec et al., 2008). Accordingly, the Jak3/ signal transducer and activator of transcription 3 (Stat3) pathway is active in the malignant T cells promoting their survival (Zhang et al., 1996; Eriksen et al., 2001; Sommer et al., 2004). "
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