Team Nailin Li

Atherothrombosis Research

Our research aims to elucidate platelet engagements, apart from thrombosis and haemostasis, in inflammatory and angiogenic/vessel remodeling mechanisms in atherosclerosis, and eventually to develop novel antiplatelet agents targeting platelet inflammatory/angiogenic activities for atherothrombotic disease treatments.

We are interested in how platelets regulate immune responses of CD4⁺ T cells and how platelet-regulated CD4⁺ T effector cell responses impact atherosclerotic development. Hence, by combining in vitro experiments with human cells, in vivo animal models, and high throughput omics analyses, we study how platelet-derived mediators, namely transforming growth factor b (TGFb) and platelet factor 4 (PF4), regulate CD4⁺ T cell activation and metabolism, phenotype development, effector cell function, and subsequently atherosclerotic lesion development.

We are also interested in the mechanisms governing differential storage and release of pro-angiogenic and anti-angiogenic factors of platelets, and how platelet distinct release of angiogenic factors influence angiogenesis. The work has expanded our research into how platelet-derived angiogenic factors regulated tumor microenvironment and cancer progression.

Teammembers

• Yanmei Lu, MD, PhD, affiliated for research
• Yanan Min, MD, PhD, affiliated for research

Research support

• The Swedish Heart-Lung Foundation
• The Swedish Research Council
• STINT
• Karolinska Institutet

Selected publications

Platelets fine-tune effector responses of naïve CD4+ T cells via platelet factor 4-regulated transforming growth factor β signaling.
Min Y, Hao L, Liu X, Tan S, Song H, Ni H, Sheng Z, Jooss N, Liu X, Malmström RE, Sun Y, Liu J, Tang H, Zhang H, Ma C, Peng J, Hou M, Li N
Cell Mol Life Sci 2022 Apr;79(5):247

Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity.
Tan S, Guo X, Li M, Wang T, Wang Z, Li C, Wu Z, Li N, Gao L, Liang X, Ma C
J Exp Med 2021 Sep;218(9):

Platelet factor 4 enhances CD4+ T effector memory cell responses via Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis.
Tan S, Li S, Min Y, Gisterå A, Moruzzi N, Zhang J, Sun Y, Andersson J, Malmström RE, Wang M, Berggren PO, Schlisio S, Liao W, Ketelhuth DFJ, Ma C, Li N
J Thromb Haemost 2020 Oct;18(10):2685-2700

Tim-3 Hampers Tumor Surveillance of Liver-Resident and Conventional NK Cells by Disrupting PI3K Signaling.
Tan S, Xu Y, Wang Z, Wang T, Du X, Song X, Guo X, Peng J, Zhang J, Liang Y, Lu J, Peng J, Gao C, Wu Z, Li C, Li N, Gao L, Liang X, Ma C
Cancer Res 2020 Mar;80(5):1130-1142

Platelet releasate promotes breast cancer growth and angiogenesis via VEGF-integrin cooperative signalling.
Jiang L, Luan Y, Miao X, Sun C, Li K, Huang Z, Xu D, Zhang M, Kong F, Li N
Br J Cancer 2017 Aug;117(5):695-703

PAR1-stimulated platelet releasate promotes angiogenic activities of endothelial progenitor cells more potently than PAR4-stimulated platelet releasate.
Huang Z, Miao X, Luan Y, Zhu L, Kong F, Lu Q, Pernow J, Nilsson G, Li N
J Thromb Haemost 2015 Mar;13(3):465-76

Platelets provoke distinct dynamics of immune responses by differentially regulating CD4+ T-cell proliferation.
Zhu L, Huang Z, Stålesen R, Hansson GK, Li N
J Thromb Haemost 2014 Jul;12(7):1156-65

Platelets regulate CD4⁺ T-cell differentiation via multiple chemokines in humans.
Gerdes N, Zhu L, Ersoy M, Hermansson A, Hjemdahl P, Hu H, Hansson GK, Li N
Thromb Haemost 2011 Aug;106(2):353-62

Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli.
Chatterjee M, Huang Z, Zhang W, Jiang L, Hultenby K, Zhu L, Hu H, Nilsson GP, Li N
Blood 2011 Apr;117(14):3907-11