“…Injection or inhalation of fibrils composed of amyloidogenic peptides as short as six amino acids from a variety of proteins induces several pathways of immune suppression, resulting in reduction of the proinflammatory cytokines IL-6, IL-1β, and TNF-α and reduction of T cell activation (7). The fibrils are bound specifically and endocytosed by peritoneal macrophages (MΦs) and B2 and B1a lymphocytes, but not T lymphocytes, mast cells, or eosinophils (8,9). The binding results in changes in gene expression, leading to several coordinated antiinflammatory responses: (i) activation of the cells, defined as an increased expression of CD83, CD80, and CD86 on the MΦs, and of CD80, CD86, CD25, and CD83 on the B1a lymphocytes; (ii) decreased expression of integrins and chemokine receptors, which allows both cell populations to traffic from the peritoneum to secondary lymph organs; and (iii) evidence of continued high expression of IL-10 in both cell types, with induced expression of CTLA4, BTLA, IRF4, and Siglec G in the B1a cells, thus increasing their immune-suppressive potential.…”