The Journal of immunology : official journal of the American Association of Immunologists
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Idiopathic pulmonary fibrosis is a fatal disease characterized by progressive destruction of the lung. Although TLR2 bridges innate and adaptive immunity by sensing tissue damage, its role in pulmonary fibrosis remains unclear. To address this issue, TLR2(-/-) and WT mice were examined for bleomycin-induced pulmonary fibrosis (BIPF). ⋯ BIPF was more severe in IL-17A(-/-) mice and in TLR2(-/-) mice treated with anti-IL-17 mAb than in TLR2(-/-) and WT mice. Furthermore, IL-27 blockade in WT mice reduced hydroxyproline levels by enhancing IL-17 production, whereas the treatment of TLR2(-/-) mice with a chemokine mixture increased hydroxyproline levels by recruiting inflammatory cells into the lungs. TLR2 signaling promotes BIPF by inducing IL-27 and chemokine production by respiratory epithelial cells, thereby inhibiting IL-17 production and recruiting inflammatory cells into the lungs.
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TOSO/FAIM3 recently has been identified as the long-sought-after FcR for IgM (FcμR). FcμR is expressed on human CD19(+) B cells, CD4(+)/CD8(+) T cells, and CD56(+)/CD3(-) NK cells and has been shown to be overexpressed in chronic lymphocytic leukemia (CLL) cells. CLL is a malignancy of mature IgM(+) B lymphocytes that display features of polyreactive, partially anergized B cells related to memory B cells. ⋯ Although it has been reported that BCR activation increases FcμR expression, we found that activation of TLRs strongly downregulated FcμR at both the mRNA and protein levels. Through internalization of IgM bound immune complexes, FcμR may play a role in immune surveillance and contribute to B cell activation. In addition, FcμR deserves study as a potential pathway for the delivery of therapeutic Ab-drug conjugates into CLL cells.