Regulation of Interleukin-10 Gene Expression in Macrophages Engulfing Apoptotic Cells

Zhang, Yan; Kim, Ha-Jeong; Yamamoto, Soichiro; Kang, Xin; Ma, Xiaojing

doi:10.1089/jir.2010.0004

Cited by 34 publications

(24 citation statements)

References 115 publications

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“…IL-10 was originally defined as a T cell cytokine, predominately secreted from Th2 T cells (13). However, it is now known that many cells, including macrophages and regulatory B cells as well as T cells, can produce IL-10 (13). IL-10 plays an important immune regulatory role, preventing inflammatory immune responses and the development of autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

“…Within the germinal center, CD68 + tingible-body macrophages are important regulators of apoptotic B cell removal (10). Apoptotic debris can trigger IL-10 production (11–13). Notably, it was recently shown that apoptotic cell infusion can induce regulatory B cells which, through their production of IL-10, can reduce the severity collagen-induced arthritis (11).…”

Section: Introductionmentioning

confidence: 99%

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Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory Cells

Getts

Turley

Smith

et al. 2011

The Journal of Immunology

183

260

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Antigen-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide antigens linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-SP) has been demonstrated to be a highly efficient method for inducing peripheral, antigen-specific T cell tolerance for treatment of autoimmune disease. However, little is understood about the mechanisms underlying this therapy. Here, we show that apoptotic Ag-SP accumulate in the splenic marginal zone where their uptake by F4/80+ macrophages induces production of IL-10 which upregulates the expression of the immunomodulatory costimulatory molecule PD-L1 which is essential for Ag-SP tolerance induction. Ag-SP infusion also induces Tregs which are dispensable for tolerance induction, but required for long-term tolerance maintenance. Collectively, these results indicate that Ag-SP tolerance recapitulates how tolerance is normally maintained in the hematopoietic compartment and highlight the interplay between the innate and adaptive immune systems in the induction of Ag-SP tolerance. We show for the first time that tolerance results from the synergistic effects of two distinct mechanisms – PD-L1-dependent T cell-intrinsic unresponsiveness and the activation of Tregs. These findings are particularly relevant as this tolerance protocol is currently being tested in a Phase I/IIa clinical trial in new-onset relapsing-remitting MS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory Cells

Getts

Turley

Smith

et al. 2011

The Journal of Immunology

183

260

View full text Add to dashboard Cite

show abstract

“…IL-10 was selected as a biomarker for immunological activities due to its crucial role in the suppression and prevention of inflammatory responses (46,47). This cytokine is produced by several immune cells, such as regulatory CD4…”

Section: Discussionmentioning

confidence: 99%

Piliation of Lactobacillus rhamnosus GG Promotes Adhesion, Phagocytosis, and Cytokine Modulation in Macrophages

García

Petrova

Claes

et al. 2015

Appl Environ Microbiol

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dRecently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili.

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“…By contacting apoptotic cells, macrophages also produce anti-inflammatory cytokines such as TGFβ and interleukin (IL)-10 (IL-10) [10,11]. TGFβ plays a role in the resolution of inflammation by inducing the production of the extracellular matrix components to initiate tissue remodeling and repair, whereas TGFβ and IL-10 are important cytokines to inhibit the synthesis and action of many inflammatory cytokines [10][11][12][13][14]. Infiltration of NK cells often occurs later than monocytes, and this migration is often modulated by the bioactive molecules produced by monocyte-derived macrophages and other cells [15,16].…”

Section: Introductionmentioning

confidence: 99%

TLRs, macrophages, and NK cells: Our understandings of their functions in uterus and ovary

Yang

Kong

Mosser

et al. 2011

International Immunopharmacology

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Regulation of Interleukin-10 Gene Expression in Macrophages Engulfing Apoptotic Cells

Cited by 34 publications

References 115 publications

Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory Cells

Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory Cells

Piliation of Lactobacillus rhamnosus GG Promotes Adhesion, Phagocytosis, and Cytokine Modulation in Macrophages

TLRs, macrophages, and NK cells: Our understandings of their functions in uterus and ovary

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