Journal of autoimmunity
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Journal of autoimmunity · Jul 2017
FcRL4+ B-cells in salivary glands of primary Sjögren's syndrome patients.
Fc receptor-like protein 4 (FcRL4) is normally expressed on a small subset of mucosa-associated B-cells, as well as on mucosa-associated lymphoid tissue (MALT) lymphoma B-cells. Primary Sjögren's syndrome (pSS) patients have an increased risk of developing MALT lymphomas, preferentially in the parotid glands. For this reason we studied here by immunohistochemistry and mRNA analysis whether FcRL4 expressing B-cells are present in salivary gland tissue (labial and parotid) of pSS patients (n = 54) and non-pSS sicca patients (n = 16) and whether parotid gland MALT lymphomas in pSS patients (n = 49) also express this receptor. ⋯ In conclusion, intraepithelial FcRL4+ B-cells are present in the salivary glands of pSS patients. These cells are likely involved in the epithelial changes seen in pSS. Their enrichment in parotid glands may explain why MALT lymphomas in pSS patients preferentially develop at this specific location.
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Journal of autoimmunity · Jul 2017
NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65.
The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hyper-inflammation during the acute phase and the hypo-inflammation during immunosuppressive phase of sepsis. However, the mechanisms for controlling hypo-inflammatory response in endotoxin tolerant macrophages remain to be fully understood. ⋯ Interestingly, cytoplasmic SIRT5 counteracted the inhibitory effects of SIRT2 and enhanced the innate inflammatory responses in macrophages and even in endotoxin-tolerant macrophages by promoting acetylation of p65 and activation of NF-κB pathway. Mechanistically, SIRT5 competed with SIRT2 to interact with NF-κB p65, in a deacetylase activity-independent way, to block the deacetylation of p65 by SIRT2, which consequently led to increased acetylation of p65 and the activation of NF-κB pathway and its downstream cytokines. Our study discovered the new functions of different Sirtuin members in sepsis, indicating that targeting of Sirtuin family members at different sepsis phases can be helpful to precisely control the progression of sepsis.