CCL3-deficient HLA-DP2 Transgenic (Tg) mice are protected against Be-induced inflammation in the lungs

Abstract Chronic beryllium disease (CBD) is an inflammatory lung disorder caused by the recruitment and expansion of pathogenic CD4 T cells. In a murine model Be-disease, we reported accumulation CCL3/Be CCL4/Be-specific cells in lungs BeO-exposed HLA-DP2 Tg mice (WT). However, addition single dose LPS on day 14 (d14) WT mice, resulted significant increase release chemokines (CCL3 CCL4), increased chemokine/Be-specific formation cellular aggregates lungs. present study, explored loss chemokine(s) CCL3/4 pathogenesis CBD using Tg-CCL3-deficient (CCL3-DP2 Tg), which were also found to be deficient CCL4. CCL3-DP2-Tg exposed BeO+LPS reduction CCL3/4/Be-specific compared mice. Also, ELISPOT assay revealed IFNγ IL-17-producing Next, examined source CCL3 majorly contributed CD11c +dendritic other hematopoietic compartment. No or little staining was observed stromal Bone marrow transfer from CCL3-DP2 showed role compartment both CCL3/4-specific after Be-exposure. Overall, that cell-derived CCL4 plays important CBD, lack protects against Be-induced damage. NIH RO1 HL152756