Cigarette smoking is an independent risk factor for onset of NAFLD.

Background & aims-Glutamine plays a protective role in intestinal cells during physiological stress, however, the protection mechanisms are not fully understood. Autophagy functions in bulk degradation of cellular components, but has been recently recognized as an important mechanism for cell survival under conditions of stress. We therefore sought if glutamine's actions involve the induction of autophagy in intestinal cells and, if so, the mechanisms that underlie this action.

Because abnormalities of mucosal immunity have been suggested in human IgA nephropathy, we examined the involvement of mucosal immunity in IgA deposition to the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for human IgA nephropathy with hyperserum IgA. The number of surface IgA+B220− lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did not show such increase. The surface IgA+B220− LP lymphocytes spontaneously secreted IgA in culture. Morphological studies showed that the surface IgA+B220− lymphocytes of murine intestinal LP are identical with plasma cells (PCs). About 20% of IgA+B220− PC in LP expressed both Mac-1 and CD19, suggesting that they may derive from peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using bromodeoxyuridine revealed no difference between HIGA mice and normal mice, suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due to enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In addition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to one forth) with aging. These data suggest that the increased number of intestinal IgA-producing PCs and the down-regulation of IgA excretion into the intestinal lumen might synergistically contribute to the hyperserum IgA in HIGA mice and resultant IgA deposition to the kidney.

The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes, Peyer's patches and well-defined lymphoid follicles in the spleen. We found that antibody responses are elicited, albeit weakly, to either T cell-dependent or T cell-independent antigen by aly/aly mutants. However, isotype switching was defective. The T cell-dependent immune response was not elicited in splenectomized aly/aly mice. Neither hypermutation nor germinal center formation was observed in aly/aly mice. These results suggest that T-B collaboration requires either lymph nodes or spleen, and that hypermutation and affinity maturation depend on germinal center formation.

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