Natural igM and TLR agonists switch murine splenic pan-B to “regulatory” cells that suppress ischemia-induced innate inflammation via regulating NKT-1 cells

Peter I. Lobo, Kailo H. Schlegel, Amandeep Bajwa, Liping Huang, Mark D. Okusa

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Abstract

Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney. Such ex vivo induced regulatory pan-B cells and BMDC express low CD1d and inhibit inflammation by regulating in vivo NKT-1 in the context of lowlipid antigen presentation and by a mechanism that requires costimulatory molecules, CD1d, PDL1/PD1, and IL10. Second, LPS and CpG have opposite effects on induction of regulatory activity in BMDC and B cells. LPS enhances regulatory activity of IgM-pretreated BMDC but negates the IgM-induced regulatory activity in B cells, while CpG, with or without IgM pretreatment, induces regulatory activity in B cells but not in BMDC. Differences in the response of pan-B and dendritic cells to LPS and CpG, especially in the presence of IgM-ALA, may have relevance during infections and inflammatory disorders where there is an increased IgM-ALA and release of TLRs 4 and 9 ligands. Ex vivo induced regulatory pan-B cells could have therapeutic relevance as these easily available cells can be pre-emptively infused to prevent AKI that can occur during open heart surgery or in transplant recipients receiving deceased donor organs.

Original languageEnglish (US)
Article number974
JournalFrontiers in immunology
Volume8
Issue numberAUG
DOIs
StatePublished - Aug 23 2017

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Regulatory B-Lymphocytes
Natural Killer T-Cells
Dendritic Cells
B-Lymphocytes
Ischemia
Inflammation
Bone Marrow
Immunoglobulin M
Autoantibodies
Leukocytes
Acute Kidney Injury
CD1d Antigen
Antigen Presentation
Inbred C57BL Mouse
Interleukin-10
Thoracic Surgery
Reperfusion
Tissue Donors
Ligands
Kidney

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Natural igM and TLR agonists switch murine splenic pan-B to “regulatory” cells that suppress ischemia-induced innate inflammation via regulating NKT-1 cells. / Lobo, Peter I.; Schlegel, Kailo H.; Bajwa, Amandeep; Huang, Liping; Okusa, Mark D.

In: Frontiers in immunology, Vol. 8, No. AUG, 974, 23.08.2017.

Research output: Contribution to journalArticle

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