The study shows that bic/microRNA-155 is essential for normal immune function. Mice lacking bic/miR-155 are immunodeficient and exhibit increased lung airway remodeling. The research demonstrates that bic/miR-155 is required for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/miR-155-deficient CD4+ T cells identified a wide range of miR-155-regulated genes, including cytokines, chemokines, and transcription factors. The study suggests that bic/miR-155 plays a key role in immune system homeostasis and function. MicroRNAs (miRNAs) regulate gene expression by binding to the 3' untranslated region (3' UTR) of genes, preventing protein accumulation by repressing translation or inducing mRNA degradation. Over 500 miRNAs have been identified in mammals, but their functions are still being elucidated. In the immune system, the enzyme Dicer is required for T cell function, suggesting regulatory roles for miRNAs in lymphocytes. One miRNA, miR-155, maps within and is processed from an exon of the noncoding RNA known as bic. Bic/miR-155 shows increased expression in activated B and T cells, as well as in activated macrophages and dendritic cells. Overexpression of bic/miR-155 has been reported in B cell lymphomas and solid tumors, and transgenic miR-155 mice have been shown to develop B cell malignancies in vivo, indicating that the locus may be linked to cancer. To define the in vivo role of bic/miR-155, mutant alleles were generated in embryonic stem cells to obtain bic-deficient mice. Bic-deficient mice were viable and fertile but developed lung pathology with age. They showed increased lung airway remodeling, increased bronchiolar subepithelial collagen deposition, and increased cell mass of subbronchiolar myofibroblasts. These changes are reminiscent of lung fibrosis that often complicates systemic autoimmune processes with lung involvement. Bic-deficient mice also developed enteric inflammation. The pathology observed in bic-deficient mice prompted the examination of the requirement of bic/miR-155 in immunity. Bic-deficient mice showed impaired protective immunity. After intravenous immunization with the live attenuated form of the enteric pathogen Salmonella typhimurium, mice were assessed for their ability to resist oral challenge with virulent S. typhimurium bacteria. Bic-deficient mice were less readily protected by aroA vaccination and succumbed to challenge with the virulent strain. This suggests that bic/miR-155 is required for protective immunity. The study also examined the in vivo B and TThe study shows that bic/microRNA-155 is essential for normal immune function. Mice lacking bic/miR-155 are immunodeficient and exhibit increased lung airway remodeling. The research demonstrates that bic/miR-155 is required for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/miR-155-deficient CD4+ T cells identified a wide range of miR-155-regulated genes, including cytokines, chemokines, and transcription factors. The study suggests that bic/miR-155 plays a key role in immune system homeostasis and function. MicroRNAs (miRNAs) regulate gene expression by binding to the 3' untranslated region (3' UTR) of genes, preventing protein accumulation by repressing translation or inducing mRNA degradation. Over 500 miRNAs have been identified in mammals, but their functions are still being elucidated. In the immune system, the enzyme Dicer is required for T cell function, suggesting regulatory roles for miRNAs in lymphocytes. One miRNA, miR-155, maps within and is processed from an exon of the noncoding RNA known as bic. Bic/miR-155 shows increased expression in activated B and T cells, as well as in activated macrophages and dendritic cells. Overexpression of bic/miR-155 has been reported in B cell lymphomas and solid tumors, and transgenic miR-155 mice have been shown to develop B cell malignancies in vivo, indicating that the locus may be linked to cancer. To define the in vivo role of bic/miR-155, mutant alleles were generated in embryonic stem cells to obtain bic-deficient mice. Bic-deficient mice were viable and fertile but developed lung pathology with age. They showed increased lung airway remodeling, increased bronchiolar subepithelial collagen deposition, and increased cell mass of subbronchiolar myofibroblasts. These changes are reminiscent of lung fibrosis that often complicates systemic autoimmune processes with lung involvement. Bic-deficient mice also developed enteric inflammation. The pathology observed in bic-deficient mice prompted the examination of the requirement of bic/miR-155 in immunity. Bic-deficient mice showed impaired protective immunity. After intravenous immunization with the live attenuated form of the enteric pathogen Salmonella typhimurium, mice were assessed for their ability to resist oral challenge with virulent S. typhimurium bacteria. Bic-deficient mice were less readily protected by aroA vaccination and succumbed to challenge with the virulent strain. This suggests that bic/miR-155 is required for protective immunity. The study also examined the in vivo B and T