CCL18-mediated pulmonary infiltration of T lymphocytes is independent of TRAIL but requires DR5 (102.20) (original) (raw)

Journal of Immunology, 2011

Abstract

Activities of T lymphocytes are centrally regulated by interactions between multiple members of the TNF/TNF-R family. TRAIL is a member of the TNF family with pro-apoptotic activity. The only signaling TRAIL receptor in mice is death receptor (DR) 5. CCL18, a chemokine with selective chemotactic activity on T lymphocytes, is known for its involvement in pulmonary inflammation and fibrosis associated with autoimmune diseases. We measured soluble TRAIL in bronchoalveolar lavage (BAL) fluids. The levels of TRAIL were significantly elevated (p < 0.01, ANOVA) in BAL from 16 patients with scleroderma lung disease (211±110 pg/ml) compared to 16 patients without lung involvement (115±58 pg/ml), or 8 healthy controls (73±41 pg/ml). To determine whether TRAIL is important for CCL18-induced pulmonary infiltration of lymphocytes, recombinant adenovirus-mediated gene delivery of CCL18 was performed in TRAIL KO, DR5 KO, and WT mice. Overexpression of CCL18 caused profound pulmonary lymphocytic infiltration in WT and TRAIL KO mice, compared to control mice infected with AdV-NULL. In contrast, infiltration of T lymphocytes was completely abrogated in CCL18-expressing DR5 KO mice, based on lung histology. Thus, the levels of TRAIL are elevated in the lungs of patients with autoimmunity-associated inflammation and fibrosis, yet TRAIL does not appear to be involved in the CCL18-mediated T lymphocytic infiltration, whereas its receptor DR5 is required for such T cell response to CCL18.

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