For a full publication list of dr. Clive McKimmie, click here for google scholar or pubmed

VHIT publications

January 22, 2020

Science Translational Medicine (2020)


Steven R Bryden,  Marieke Pingen,  Daniella A Lefteri, Janne Miltenburg, Leen Delang, Sofie Jacobs, Rana Abdelnabi, Johan Neyts, Emilie Pondeville, Jack Major, Marietta Muller, Henna Khalid, Andrew Tuplin, Margus Varjak, Andres Merits, Julia Edgar, Gerard J Graham, Kave Shams and Clive S McKimmie.

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Mosquito Biting Modulates Skin Response to Virus Infection

May 07, 2017

Marieke Pingen*, Michael A. Schmid*, Eva Harris, and Clive S. McKimmie (*contributed equally)

Trends in Parasitology

Mosquitoes do not just passively transfer virus from one individual to another, but host responses to mosquito-derived factors impact infection and disease, aiding replication and dissemination within the host. In this review we discuss the latest research about this fascinating interplay between mosquito, virus, and the mammalian host.

Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection

June 20, 2016

Marieke Pingen, Steven R. Bryden, Emilie Pondeville, Esther Schnettler, Alain Kohl, Andres Merits, John K. Fazakerley, Gerard J. Graham, Clive S. McKimmie.



Mosquito bites are not only annoying, they enhance virus replication and dissemination, increasing mortality of their mammalian hosts. We found that this is due to neutrophil-drien inflammation which retains the virus in the skin and drives macrophage recruitment. Both recruited and resident myeloid cells become infected and contribute to local viral replication. Blocking of this leukocyte recruitment to the mosquito bite site inhibits viral infection.

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Other great work we have been involved with


MicroRNA-146 and cell trauma down-regulate expression of the psoriasis-associated atypical chemokine receptor ACKR2

February 23, 2018

J Biol Chem. 2018 Feb 23;293(8):3003-3012.

Chemokines are the principal regulators of leukocyte migration and are essential for initiation and maintenance of inflammation. Atypical chemokine receptor 2 (ACKR2) binds and scavenges proinflammatory CC-chemokines, regulates cutaneous T-cell positioning, and limits the spread of inflammation in vivo Altered ACKR2 function has been implicated in several inflammatory disorders, including psoriasis, a common and debilitating T-cell-driven disorder characterized by thick erythematous skin plaques. ACKR2 expression is abnormal in psoriatic skin, with decreased expression correlating with recruitment of T-cells into the epidermis and increased inflammation. However, the molecular mechanisms that govern ACKR2 expression are not known. Here, we identified specific psoriasis-associated microRNAs (miRs) that bind ACKR2, inhibit its expression, and are active in primary cultures of human cutaneous cells. Using both in silico and in vitro approaches, we show that miR-146b and miR-10b directly bind the ACKR2 3'-UTR and reduce expression of ACKR2 transcripts and protein in keratinocytes and lymphatic endothelial cells, respectively. Moreover, we demonstrate that ACKR2 expression is further down-regulated upon cell trauma, an important trigger for the development of new plaques in many psoriasis patients (the Koebner phenomenon). We found that tensile cell stress leads to rapid ACKR2 down-regulation and concurrent miR-146b up-regulation. Together, we provide, for the first time, evidence for epigenetic regulation of an atypical chemokine receptor. We propose a mechanism by which cell trauma and miRs coordinately exacerbate inflammation via down-regulation of ACKR2 expression and provide a putative mechanistic explanation for the Koebner phenomenon in psoriasis.

Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2

August 25, 2016

Shams KWilson GJSingh Mvan den Bogaard EHLe Brocq MLHolmes SSchalkwijk JBurden ADMcKimmie CSGraham GJ.

Journal of Investigative Dermatology 

In this paper Clive helped Dr. Kave Shams to study the role of ACKR2 in psoriasis. The results have important implications for the understanding of the impact of spatial restriction on the spread of inflammatory lesions and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases.

The picture shows migration of T cells in the presence of CCL5 and ACKR2-expressing keratinocytes. 

September 13, 2014

Michlmayr, D., McKimmie, C. S*., Pingen, M., Haxton, B., Mansfield K., Johnson N., Fooks A.R., Graham G.J.

*co-corresponding author.   

Journal of Virology

This paper by Daniela Michlmayr, in collaboration with Gerry Graham, defines the mechanism by which inflammatory leukocytes enter the virus infected brain.  Blockade of the chemokine pathways involved prevented leukocyte entry and counter-intuitively helped increase survival to an otherwise lethal infection.

Picture shows T cells (brown) infiltrating the meninges

An analysis of the function and expression of D6 on lymphatic endothelial cells.

May 01, 2013

McKimmie, C. S., Singh, M. D., Hewit, K., Lopez-Franco, O., Le Brocq, M., Rose-John, S., Lee K.M., Baker A.H., Wheat R., Blackbourn D.J., Nibbs R.J., Graham G.J.



This paper demonstrates that the atypical chemokine receptor ACRK2 (formally called D6) prevents inappropriate associations between lymphatic vessels and inflammatory myeloid cells and immature dendritic cells. Interestingly, the HIV associated Karposi sarcoma demonstrates exceptionally high ACKR2 expression, which likely acts to suppresses inflammatory chemokine responses. Pictured is a lymphatic vessel stained in red (podoplanin) and green (ACKR2/D6).

D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion.

December 01, 2011

Lee, K. M., McKimmie, C. S*., Gilchrist, D. S., Pallas, K. J., Nibbs, R. J., Garside, P., McDonald V., Jenkins C., Ransohoff R., Liu L., Milling S., Cerovic V., Graham G.J.

*co-first author



Here we show that the atypical chemokine receptor ACKR2 (D6) acts in vivo to control interactions between stromal lymphatic endothelial cells and inflammatory leukocytes. Without ACKR2, lymphatics can become congested and overloaded with inflammatory leukocytes such as immature dendritic cells and myeloid cells, resulting in edema.  Importantly, this results in a reduced migration of dendritic cells from inflamed sites to the draining lymph node, which may have consequences for the proper initiation of adaptive immune responses. 

Pictured is a lymphatic vessel (yellow) that lacks ACKR2 expression and consequently becomes decorated with inflammatory immature dendritic cells (red and green)

A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration

December 01, 2009

McKimmie, C. S., Moore, M., Fraser, A. R., Jamieson, T., Xu, D., Burt, C., Pitman N.I., Nibbs R.J., McInnes I.B., Liew F.Y., Graham G.J.



Here we show that systemic administration of an inflammatory TLR2 ligands can counter-intuitively prevent the development of psoriasis-like inflammation in the skin. We demonstrate that TLR2 ligands alter the ability of leukocytes to respond to chemotactic cues that would otherwise guide them to inflamed skin, and instead redirect their migration to lymphoid tissue. Picture shows lymphatic cells and leukocytes in co-culture for display purposes.

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