TY - JOUR AU - Vieyra-Garcia, Pablo AU - Crouch, Jack D. AU - O’Malley, John T. AU - Seger, Edward W. AU - Yang, Chao H. AU - Teague, Jessica E. AU - Vromans, Anna Maria AU - Gehad, Ahmed AU - Win, Thet Su AU - Yu, Zizi AU - Lowry, Elizabeth L. AU - Na, Jung-Im AU - Rook, Alain H. AU - Wolf, Peter AU - Clark, Rachael A. T1 - Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma PY - 2019/01/10/ AB - Psoralen plus UVA (PUVA) is an effective therapy for mycosis fungoides (MF), the skin-limited variant of cutaneous T cell lymphoma (CTCL). In low-burden patients, PUVA reduced or eradicated malignant T cells and induced clonal expansion of CD8+ T cells associated with malignant T cell depletion. High-burden patients appeared to clinically improve but large numbers of malignant T cells persisted in skin. Clinical improvement was linked to turnover of benign T cell clones but not to malignant T cell reduction. Benign T cells were associated with the Th2-recruiting chemokine CCL18 before therapy and with the Th1-recruiting chemokines CXCL9, CXCL10, and CXCL11 after therapy, suggesting a switch from Th2 to Th1. Inflammation was correlated with OX40L and CD40L gene expression; immunostaining localized these receptors to CCL18-expressing c-Kit+ dendritic cells that clustered together with CD40+OX40+ benign and CD40+CD40L+ malignant T cells, creating a proinflammatory synapse in skin. Our data suggest that visible inflammation in CTCL results from the recruitment and activation of benign T cells by c-Kit+OX40L+CD40L+ dendritic cells and that this activation may provide tumorigenic signals. Targeting c-Kit, OX40, and CD40 signaling may be novel therapeutic avenues for the treatment of MF. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.124233 VL - 4 IS - 1 UR - https://doi.org/10.1172/jci.insight.124233 PB - The American Society for Clinical Investigation ER -