TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients1

• Published in: The Journal of immunology (1950) Vol. 183; no. 11; pp. 7461 - 7470
• Main Authors: Jagannathan, Madhumita, Hasturk, Hatice, Liang, YanMei, Shin, Hyunjin, Hetzel, Jeremy T., Kantarci, Alpdogan, Rubin, Daniel, McDonnell, Marie E., Van Dyke, Thomas E., Ganley-Leal, Lisa M., Nikolajczyk, Barbara S.
• Format: Journal Article
• Language: English
• Published: 16.11.2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0901517

Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1β and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-α) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation.