Tag Archives: B cells

B Cells and Lactate Slow Down the Immune Response

Sodium lactate
A simple injection of sodium lactate can influence inflammasome activation.
This week on TIBDI: IL-35-secreting B cells inhibit immune responses; lactate interferes with inflammasome activation; and mucus and microbiota link nature and nurture.

New Inhibitory B Cells

B cells, known more for their antibody producing potential, also have a regulatory function when they secrete the anti-inflammatory cytokine interleukin (IL)-10. In a recent publication of Nature, Ping Shen and Toralf Roch of the German Rheumatology Research Center (DRFZ) in Germany discovered that IL-35-secreting B cells also play a similar role. They found that triggering co-stimulatory receptors on B cells induced IL-35 production and that IL-35-deficient B cells both hindered the recovery from a model of autoimmune disease (multiple sclerosis) and increased the immune response to an intestinal pathogen (Salmonella). Given the widespread influence of IL-35 producing B cells during infection and inflammatory disease, it will be interesting to see if they also are important for inflammatory bowel disease (IBD).

Lactate Slows Down Inflammasomes

Previous literature has indicated that the NLRP3 inflammasome is associated with Crohn’s disease (CD), and may be needed to induce protective immune responses against invading bacteria. Inflammasomes in macrophages are activated, in part, by danger signals. While danger signals mainly induce pro-inflammatory cytokine production, they also stimulate metabolic pathways, and one product that is produced is lactate. According to results produced by Rafaz Hoque of Yale University, lactate can function as a negative regulator of inflammasome activation. The team at Yale found that stimulation of the lactate receptor GPR81 could modify Toll-like receptor 4 signaling and lower subsequent NLRP3 activation. In vivo, lactate was effective at reducing acute organ injury in models with potent inflammasome activation, such as hepatitis and pancreatitis. This could mean that lactate modulates NLRP3 responses in Crohn’s disease as well.

Nature, Nurture and Mucus Production

Intestinal mucus has the important function of preventing bacterial contact with the epithelial surface. In fact, TMF-/- mice lacking a specific Golgi-associated protein (TMF/ARA160), which produce thick mucus, are generally protected from experimental colitis. However, Shai Bel of the Bar Ilan University in Israel has found that the protection is not derived from mucus alone. The intestinal microbiota are also important. The team found that the microbiota of TMF-/- mice is different from that of wild-types, and has larger populations of bacteria from the Firmicutes phylum. Even more importantly, transfer of these populations to normal mice, by co-housing, also transferred the colitis protection. This underscores the potential role of microbiota manipulation in lowering IBD susceptibility despite genetic predisposition.

Q: What’s your opinion about microbiota manipulation for IBD prevention? Feel free to contribute your thoughts here or on the LinkedIn discussion group.

References

Helminths and Peritoneal B Cells Reduce Colitis

Heligmosomoides
Heligmosomoides polygyrus bakeri. This murine intestinal parasite induces colon regulatory T cells.
This week reveals two interesting inflammatory bowel disease-related studies published in the Journal of Immunology. One shows how parasites can induce potent colon regulatory T cells, and the other describes the importance of peritoneal B cells in regulating inflamed intestines. For both articles, interleukin-10 plays a critical role.

Helminth Infections Induce Colon Protective Regulatory T Cells

Helminths have the ability to reduce harmful inflammation, and they are now being tested as therapeutic agents for inflammatory bowel disease in clinical trials. Using a helminth found in mice, Heligmosomoides polygyrus bakeri, scientists from Tufts attempted to learn how these parasites performed their function in the intestines. They found that the helminths increased the number of Foxp3+ regulatory T cells in the colons of host mice and increased their expression of interleukin-10 (IL-10). These regulatory T cells were capable of preventing experimental colitis in an IL-10 dependent manner.

IL-10 Expressing B Cells in the Peritoneal Cavity Modulate Colitis

B cells come in many types and are present at many locations of the body. Within the main abdominal cavity, called the peritoneal cavity, many types of B cells are found, including IL-10 producing ones called B10 cells. Scientists from Duke found that these B cells also play an important role in colitis by lowering the severity of the inflammation. The production of IL-10 by these B cells significantly reduced disease severity in spontaneous and induced models of colitis by regulating neutrophil infiltration, Th1 cells, and proinflammatory cytokine production.

Do you think that interleukin-10 is the über-cytokine needed to control inflammatory bowel disease? Let us know in the comments below!

References

Hang L, Blum AM, Setiawan T, Urban JP Jr, Stoyanoff KM, Weinstock JV. Heligmosomoides polygyrus bakeri Infection Activates Colonic Foxp3+ T Cells Enhancing Their Capacity To Prevent Colitis. J Immunol. 2013 Aug 15;191(4):1927-34. doi: 10.4049/jimmunol.1201457. Epub 2013 Jul 12.

Maseda D, Candando KM, Smith SH, Kalampokis I, Weaver CT, Plevy SE, Poe JC, Tedder TF. Peritoneal Cavity Regulatory B Cells (B10 Cells) Modulate IFN-γ+CD4+ T Cell Numbers during Colitis Development in Mice. J Immunol. 2013 Aug 5. [Epub ahead of print]