Dataset Information

A shift towards pro-inflammatory CD16+ monocyte subsets with preserved cytokine production potential after kidney transplantation.

ABSTRACT:

Background

The presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.

Methods

Phenotype, activation status and cytokine production capacity of classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++), monocytes were determined by flow cytometry in a cohort of 33 healthy individuals, 30 renal transplant recipients at transplantation, 19 recipients at 3 months and 16 recipients at 6 months after transplantation using a cross-sectional approach.

Results

The percentage of both CD16+ monocyte subsets was significantly increased in transplant recipients compared to healthy individuals, indicative of triggered innate immunity (p?0.039). Enhanced production capacity of tumor necrosis factor-?, interferon-? and interleukin-1? was observed by monocytes at transplantation compared to healthy individuals. Remarkably, three months post-transplant, in presence of potent immunosuppressive drugs and despite improved kidney function, interferon-?, tumor necrosis factor-? and interleukin-10 production capacity still remained significantly increased.

Conclusion

Our data demonstrate a skewed balance towards pro-inflammatory CD16+ monocytes that is present at the time of transplantation and retained for at least 6 months after transplantation. This shift could be one of the important drivers of early post-transplant cellular immunity.

SUBMITTER: Vereyken EJ

PROVIDER: S-EPMC3726371 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

A shift towards pro-inflammatory CD16+ monocyte subsets with preserved cytokine production potential after kidney transplantation.

Vereyken Elly J F EJ Kraaij Marina D MD Baan Carla C CC Rezaee Farhad F Weimar Willem W Wood Kathryn J KJ Leenen Pieter J M PJ Rowshani Ajda T AT

PloS one 20130729 7

<h4>Background</h4>The presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.<h4> ...[more]

PMID: 23922945

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Project description:BackgroundHuman peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCgammaRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CD16 and CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including sepsis and HIV infection.ResultsTo gain insight into the developmental relationship and functions of CD16+ and CD16- Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16+ compared to CD16- Mo. CD16+ Mo were distinguished by upregulation of transcripts for dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (MPhi) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16- Mo were distinguished by upregulation of transcripts for myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential expression of CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1 was confirmed by flow cytometry. Furthermore, increased expression of RARA and KLF2 transcripts in CD16+ Mo coincided with absence of cell surface cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing.ConclusionThese results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MPhi - and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MPhi in vivo.

Dataset Information

A shift towards pro-inflammatory CD16+ monocyte subsets with preserved cytokine production potential after kidney transplantation.

Background

Methods

Results

Conclusion

Publications

A shift towards pro-inflammatory CD16+ monocyte subsets with preserved cytokine production potential after kidney transplantation.

Similar Datasets

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