Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells

Abstract Background and Aims Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end- stage renal disease. It has been postulated that interleukin-10 (IL-10)-producing Regulatory B cells (Breg) play an important role for the tissue repairment in several tissues and organs. Basically, protective role of Breg has been reported in inflammatory bowel disease. In the kidney, it has been shown that IL-10 suppresses renal function decline and improves renal prognosis in IRI model, a typical model of AKI. However, the identity of Breg in the kidney and their origin have not been clarified. Further, how the Breg works during the transition from AKI to CKD is not known. Therefore, first we investigated whether Breg existed in renal tissue on the progression from AKI to CKD in IRI model mice. Further, we performed splenectomy, and examined the renal injury, Breg, and plasma IL-10 levels in this model. Method To examine the existence of Breg in the kidney of IRI model, we used 8-10 weeks-old GFP / IL-10 mice based on C57BL / 6J mice. They are reporter mice for IL-10 producing cells, and can visualize IL-10 producing cells under a fluorescence microscope without fluorescent immunostaining. We prepared following three groups, sham, IRI (unilateral), and IRI + SN (splenectomy) groups. Mice were anesthetized with chloral hydrate (4 g/kg,, intraperitoneal). After making a midline incision, exposed a blood vessel of the left renal pedicles and clamped it for 30 min by clips. one day, 7 days, and 14 days after the surgery, mice were sacrificed, and renal function and plasma IL-10 levels as well as tissue damages by PAS and Masson’s Trichrome staining were assessed. Tissue IL-10-producing cells were detected by flow cytometry. Results There was no difference of plasma IL-10 levels and renal tubulointerstitial injury in IRI group and IRI+SN group on day 1 after IRI. However, on day 7 and day 14, plasma IL-10 levels became gradually higher in IRI group, and SN decreased the increase in IL-10 levels. Tubulointerstitial injury was induced by IRI and SN further worsened tubular damages. Serum Cr and BUN levels were not different in three groups due to normal right kidney. On day 1, number of IL-10-producing B cells increased in the spleen and renal medulla in IRI group confirmed by flow cytometry, which was completely diminished by SN, suggesting that origin of the infiltrated Breg might be spleen, thereby being involved in the protective role in IRI injury in the kidney. Conclusion We report for the first time that Breg might be recruited from spleen by AKI, which may be one of the mechanisms to prevent the progression to CKD.

Download Full-text

The Roles of Regulatory B Cells in Cancer

Journal of Immunology Research ◽

10.1155/2014/215471 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Yan He ◽

Hongyan Qian ◽

Yuan Liu ◽

Lihua Duan ◽

Yan Li ◽

...

Keyword(s):

B Cells ◽

Immune Cells ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Autoimmune Disorder ◽

Interleukin 10 ◽

Regulatory B Cells ◽

Experimental Conditions ◽

Growth Factor Beta ◽

Cytokines Secretion

Regulatory B cells (Bregs), a newly described subset of B cells, have been proved to play a suppressive role in immune system. Bregs can inhibit other immune cells through cytokines secretion and antigen presentation, which give them the role in the pathogenesis of autoimmune diseases and cancers. There are no clear criteria to identify Bregs; different markers were used in the different experimental conditions. Massive researches had described the functions of immune cells such as regulatory T cells (Tregs), dendritic cells (DCs), and B cells in the autoimmune disorder diseases and cancers. More and more researches focused on the roles of Bregs and the cytokines such as Interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) secreted by Bregs. The aim of this review is to summarize the characteristics of Bregs and the roles of Bregs in cancer.

Download Full-text

Interleukin-10 expressing regulatory B cells are decreased in blood of smokers and COPD patients

10.1183/13993003.congress-2021.pa833 ◽

2021 ◽

Author(s):

Merel Jacobs ◽

Sven Verschraegen ◽

Bihiyga Salhi ◽

Guy Brusselle ◽

Ken Bracke

Keyword(s):

B Cells ◽

Interleukin 10 ◽

Regulatory B Cells ◽

Copd Patients

Download Full-text

Potential Role for Regulatory B Cells as a Major Source of Interleukin-10 in Spleen fromPlasmodium chabaudi-Infected Mice

Infection and Immunity ◽

10.1128/iai.00016-18 ◽

2018 ◽

Vol 86 (5) ◽

Author(s):

Xue Han ◽

Ji Yang ◽

Yitong Zhang ◽

Yalin Zhang ◽

Hongtao Cao ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Potential Role ◽

Interleukin 10 ◽

Surface Markers ◽

Regulatory B Cells ◽

Plasmodium Chabaudi ◽

Impact On Survival ◽

And Function ◽

Stimulation Of

ABSTRACTInterleukin-10 (IL-10)-producing regulatory B (Breg) cells were found to be induced in a variety of infectious diseases. However, its importance in the regulation of immune response to malaria is still unclear. Here, we investigated the dynamics, phenotype, and function of Breg cells usingPlasmodium chabaudi chabaudiAS-infected C57BL/6 and BALB/c mice. BALB/c mice were more susceptible to infection and had a stronger IL-10 response in spleen than C57BL/6 mice. Analysis of the surface markers of IL-10-producing cells with flow cytometry showed that CD19+B cells were one of the primary IL-10-producing populations inP. c. chabaudiAS-infected C57BL/6 and BALB/c mice, especially in the latter one. The Breg cells had a heterogeneous phenotype which shifted during infection. The well-established Breg subset, CD19+CD5+CD1dhicells, accounted for less than 20% of IL-10-producing B cells in both strains during the course of infection. Most Breg cells were IgG+and CD138−from day 0 to day 8 postinfection. Adoptive transfer of Breg cells to C57BL/6 mice infected withP. c. chabaudiAS led to a transient increase of parasitemia without an impact on survival rate. Our finding reveals that B cells play an active and important regulatory role in addition to mediating humoral immunity in immune response against malaria, which should be paid more attention in developing therapeutic or vaccine strategies against malaria involving stimulation of B cells.

Download Full-text