[PubMed] [Google Scholar] 68. pathogen clearance. For instance, in bacterial infections such as tuberculosis (TB), caused by infection. 128 Similarly, in fungal infections such as Moclobemide pneumocystis pneumonia (PCP), an increase in IL\10\producing Bregs has been associated with the inhibition of Th1/Th17 responses and effective pathogen clearance. 129 Overall, it appears that immunosuppressive functions of Bregs can be either detrimental or beneficial depending on the disease context. 4.3. Allergic airway inflammation Asthma is chronic inflammation of the airway characterized by heightened reactivity and sensitivity of the airway to a variety of inhaled stimuli. 130 Moclobemide Bregs play a protective role against hyperresponsive airway inflammation, where IL\10\producing B cells significantly suppress inflammatory reactions. 131 Functional impairments in Bregs have been associated with enhanced asthma\like inflammation and airway hyperresponsiveness. In mouse models of disease, adoptive transfer of CD9+ Bregs suppress all asthma\related features by inhibiting effector T cells in an IL\10\dependent manner. 132 In addition, IL\10\producing CD5+CD21hiCD1dhi Bregs can reverse allergic airway inflammation by actively recruiting immunosuppressive Tregs to the lungs. 133 Interestingly, infection with Schistosoma mansoni?worms has been shown to protect against ovalbumin\induced allergic airway inflammation by inducing IL\10\producing T2\MZP Bregs. 134 In contrast with hypersensitivity, pathology in chronic obstructive pulmonary disorder (COPD) is a result of proteolytic destruction of the extracellular lung matrix by the immune response. 135 The main symptoms of COPD include chronic coughing, sputum production, and breathing difficulties. COPD patients have elevated frequencies of B cells and ELTs in their lungs 5 ; however, the role of Bregs in disease pathogenesis remains unknown. Unpublished studies from our laboratory identify an expansion of Tim\1+ and IL\10+ Bregs in the lung of COPD patients, supporting a plausible for Bregs in modulating inflammation in disease. Idiopathic pulmonary fibrosis (IPF) is a rare form of chronic and progressive fibrosing lung disease that is characterized by an increase in collagen deposition in the lung parenchyma; it is a type of interstitial lung disease (ILD). 136 In IPF, inhaled environmental pollutants (organic and inorganic dust) and toxins from cigarette smoke (CS) are implicated factors in the disease etiology, since by\products of these factors are frequently identified in the lungs of patients with this disease. 136 Ectopic lymphoid structures are commonly Moclobemide seen in lung biopsies of patients with IPF; however, the role of B cells in disease pathogenesis remains ill\defined. 86 Recent evidence suggests there is a significant decrease in CD24hiCD27+Bregs in IPF patients, mirrored by an increase in Tfh cells and levels of BAFF in the lungs and in circulation. 137 This suggests that a lack Moclobemide of Breg\mediated immunosuppression and expansion of effector B cells (Beffs) likely contribute to Moclobemide disease pathogenesis. 4.4. Autoimmunity Autoimmune diseases, including SLE, RA, SSc, and Sjogren’s syndrome, can often result in pulmonary manifestations. 138 Multiple studies have identified increased infiltration of B Rabbit polyclonal to Ki67 cells in lung tissues of patients, indicating a plausible role for B cells in disease pathogenesis. 1 Although the involvement of Bregs in lung pathology remains largely uninvestigated, numerical and functional defects in circulating Bregs have been reported in patients with SLE, SSc, RA and Sjogren’s syndrome, and found to associated with disease severity. 9 , 32 , 48 , 139 Whether the defects in Bregs are a cause or consequence of chronic inflammation remains to be addressed. In systemic autoimmune diseases, such as SLE and SSc, reduced frequencies of circulating CD24hiCD27+ and CD24hiCD38hi Bregs have been reported in patients compared to controls. 9 , 32 Numerical problems are accompanied by jeopardized Breg functions with a significant decrease in IL\10 manifestation. Importantly, B cells infiltrates have been recognized in the lung of SSc individuals with ILD and in mouse models of pulmonary lupus. 93 , 140 Improved infiltration of CD20+ B cells and plasma cells have also been reported in lung biopsies of RA individuals with interstitial pneumonia, compared to normal lungs. 141 While the phenotype of lung\infiltrating B cells remains unknown, reduced frequencies of circulating IL\10+ Breg subsets have been reported in RA individuals compared to settings and found to correlate with disease severity. 48 , 142 These problems are associated with an growth of pro\inflammatory effector B and T cells leading to exacerbated disease symptoms. Due to.