scholarly journals Cell scientist to watch – Tim Lämmermann

2021 ◽  
Vol 134 (21) ◽  
Keyword(s):  
Population Dynamics ◽  
Cell Migration ◽  
Infectious Diseases ◽  
Immune Cells ◽  
Immune Cell ◽  
Group Leader ◽  
Molecular Medicine ◽  
Max Planck ◽  
Immune Cell Migration

ABSTRACT Tim Lämmermann studied molecular medicine at the Friedrich-Alexander-University, Erlangen-Nuremberg, Germany and the Lund University, Sweden. He then joined the lab of Michael Sixt at the Max Planck Institute of Biochemistry in Martinsried, where he earned his PhD in 2009 for studying the role of integrins and cytoskeletal forces in immune cell migration. Tim then moved to the National Institute of Allergy and Infectious Diseases in Bethesda, USA for his postdoc with Ron Germain. There, he worked on the mechanisms of neutrophil swarming during infection, and received the Robert-Koch Postdoctoral Award in 2014. Since 2015, Tim has been a Group Leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, where his lab investigates the single-cell and population dynamics of immune cells. He was awarded an ERC Starting Grant in 2016.

scholarly journals Key chemokines direct migration of immune cells in solid tumors

2021 ◽  
Author(s):  
Karan Kohli ◽  
Venu G. Pillarisetty ◽  
Teresa S. Kim
Keyword(s):  
Solid Tumors ◽  
Immune Cells ◽  
Chemokine Receptors ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Chemokine Signaling ◽  
Immune Cell Migration ◽  
Preclinical And Clinical Studies ◽  
Immunosuppressive Cells

AbstractImmune cell infiltration into solid tumors, their movement within the tumor microenvironment (TME), and interaction with other immune cells are controlled by their directed migration towards gradients of chemokines. Dysregulated chemokine signaling in TME favors the growth of tumors, exclusion of effector immune cells, and abundance of immunosuppressive cells. Key chemokines directing the migration of immune cells into tumor tissue have been identified. In this review, we discuss well-studied chemokine receptors that regulate migration of effector and immunosuppressive immune cells in the context of cancer immunology. We discuss preclinical models that have described the role of respective chemokine receptors in immune cell migration into TME and review preclinical and clinical studies that target chemokine signaling as standalone or combination therapies.

scholarly journals Bone resorption: supporting immunometabolism

2018 ◽  
Vol 14 (2) ◽  
pp. 20170783 ◽  
Author(s):  
Gustav van Niekerk ◽  
Megan Mitchell ◽  
Anna-Mart Engelbrecht
Keyword(s):  
Bone Resorption ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Peripheral Tissues ◽  
Metabolic Substrates ◽  
Functional Value ◽  
Immune Cell Migration

Activation of the immune system is associated with an increase in the breakdown of various peripheral tissues, including bone. Despite the widely appreciated role of inflammatory mediators in promoting bone resorption, the functional value behind this process is not completely understood. Recent advances in the field of immunometabolism have highlighted the metabolic reprogramming that takes place in activated immune cells. It is now believed that the breakdown of peripheral tissue provides metabolic substrates to fuel metabolic anabolism in activated immune cells. We argue that phosphate, liberated by bone resorption, plays an indispensable role in sustaining immune cell metabolism. The liberated phosphate is then incorporated into macromolecules such as nucleotides and phospholipids, and is also used for the phosphorylation of metabolites (e.g. glycolytic intermediates). In addition, magnesium, also liberated during the breakdown of bone, is an essential cofactor required by various metabolic enzymes which are upregulated in activated immune cells. Finally, calcium activates various additional molecules involved in immune cell migration. Taken together, these factors suggest a key role for bone resorption during infection.

Finding a Way Out: S1P Signaling and Immune Cell Migration

2020 ◽  
Vol 38 (1) ◽  
pp. 759-784 ◽  
Author(s):  
Audrey A.L. Baeyens ◽  
Susan R. Schwab
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Clinical Trials ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Sphingosine 1 Phosphate ◽  
Immune Cell Migration

The signaling lipid sphingosine 1-phosphate (S1P) plays critical roles in an immune response. Drugs targeting S1P signaling have been remarkably successful in treatment of multiple sclerosis, and they have shown promise in clinical trials for colitis and psoriasis. One mechanism of these drugs is to block lymphocyte exit from lymph nodes, where lymphocytes are initially activated, into circulation, from which lymphocytes can reach sites of inflammation. Indeed, S1P can be considered a circulation marker, signaling to immune cells to help them find blood and lymphatic vessels, and to endothelial cells to stabilize the vasculature. That said, S1P plays pleiotropic roles in the immune response, and it will be important to build an integrated view of how S1P shapes inflammation. S1P can function so effectively because its distribution is exquisitely tightly controlled. Here we review how S1P gradients regulate immune cell exit from tissues, with particular attention to key outstanding questions in the field.

scholarly journals Pannexin Channel Regulation of Cell Migration: Focus on Immune Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Paloma A. Harcha ◽  
Tamara López-López ◽  
Adrián G. Palacios ◽  
Pablo J. Sáez
Keyword(s):  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Adenine Nucleotide ◽  
Cell Communication ◽  
Negative Regulator ◽  
General Mechanism ◽  
Current Evidence ◽  
Inflammatory Conditions

The role of Pannexin (PANX) channels during collective and single cell migration is increasingly recognized. Amongst many functions that are relevant to cell migration, here we focus on the role of PANX-mediated adenine nucleotide release and associated autocrine and paracrine signaling. We also summarize the contribution of PANXs with the cytoskeleton, which is also key regulator of cell migration. PANXs, as mechanosensitive ATP releasing channels, provide a unique link between cell migration and purinergic communication. The functional association with several purinergic receptors, together with a plethora of signals that modulate their opening, allows PANX channels to integrate physical and chemical cues during inflammation. Ubiquitously expressed in almost all immune cells, PANX1 opening has been reported in different immunological contexts. Immune activation is the epitome coordination between cell communication and migration, as leukocytes (i.e., T cells, dendritic cells) exchange information while migrating towards the injury site. In the current review, we summarized the contribution of PANX channels during immune cell migration and recruitment; although we also compile the available evidence for non-immune cells (including fibroblasts, keratinocytes, astrocytes, and cancer cells). Finally, we discuss the current evidence of PANX1 and PANX3 channels as a both positive and/or negative regulator in different inflammatory conditions, proposing a general mechanism of these channels contribution during cell migration.

scholarly journals Characterization of immune cell migration using microfabrication

2021 ◽  
Author(s):  
Doriane Vesperini ◽  
Galia Montalvo ◽  
Bin Qu ◽  
Franziska Lautenschläger
Keyword(s):  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Advantages And Disadvantages ◽  
Infected Cells ◽  
Immune Cell Migration ◽  
Underlying Mechanisms

AbstractThe immune system provides our defense against pathogens and aberrant cells, including tumorigenic and infected cells. Motility is one of the fundamental characteristics that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors, even in the absence of external treatments. These processes are termed “immune surveillance.” Migration disorders of immune cells are related to autoimmune diseases, chronic inflammation, and tumor evasion. It is therefore essential to characterize immune cell motility in different physiologically and pathologically relevant scenarios to understand the regulatory mechanisms of functionality of immune responses. This review is focused on immune cell migration, to define the underlying mechanisms and the corresponding investigative approaches. We highlight the challenges that immune cells encounter in vivo, and the microfabrication methods to mimic particular aspects of their microenvironment. We discuss the advantages and disadvantages of the proposed tools, and provide information on how to access them. Furthermore, we summarize the directional cues that regulate individual immune cell migration, and discuss the behavior of immune cells in a complex environment composed of multiple directional cues.

scholarly journals MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Stephanie Maia Acuña ◽  
Lucile Maria Floeter-Winter ◽  
Sandra Marcia Muxel
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Small Rnas ◽  
Immune Cell ◽  
Fine Tuning ◽  
Biological Processes ◽  
Host Interactions ◽  
The Past ◽  
Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

scholarly journals FRI0136 PERIPHERAL PROTEIN BIOMARKER CHANGES FOLLOWING SELECTIVE INHIBITION OF JANUS KINASE 1 (JAK1) BY FILGOTINIB IN ADULTS WITH MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH PRIOR INADEQUATE RESPONSE TO METHOTREXATE (FINCH1)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 650.2-651
Author(s):  
P. C. Taylor ◽  
E. Elboudwarej ◽  
B. Downie ◽  
J. Liu ◽  
R. E. Hawtin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Active Rheumatoid Arthritis ◽  
Immune Cell ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Bone Biology ◽  
Janus Kinase 1 ◽  
Immune Cell Migration ◽  
Dose Dependent

Background:Filgotinib (FIL), an oral selective Janus kinase 1 (JAK1) inhibitor has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA), including those with prior inadequate response to methotrexate (MTX) therapy (FINCH1;NCT02889796).Objectives:A longitudinal study of protein biomarkers related to JAK signaling1, bone biology2, immune cell migration2, and inflammation2was conducted to identify RA-associated markers altered by FIL vs MTX or adalimumab (ADA).Methods:FINCH1 RA patients (pts) were randomized to receive either a stable dose of MTX with placebo (PBO+MTX), ADA+MTX, and either FIL100mg+MTX or FIL200mg+MTX, once daily. Plasma, serum, and urine samples were taken from a subset of pts (~548) at baseline (BL) and weeks (wks) 4 and 12. Twenty-six pre-defined cytokines (biomarkers) were evaluated using ELISA. BL correlation between biomarkers and clinical response measures (DAS28CRP, SJC28, TJC28, CDAI, Patient Assessment and FACIT), were analyzed by Spearman Rank. Multiscale bootstrap resampling evaluated significant intra-cluster biomarker membership. Mean changes in biomarker levels from BL to wks 4 and 12 were compared between arms using PBO-adjusted estimates from a linear mixed effects model. A 5% false-discovery rate was applied for all analyses.Results:At BL, distinct biomarker-based pt clusters (CL) were identified. The strongest intra-group correlations were in bone-cartilage resorption/inflammation (CL1; Rho range 0.37–0.88) and JAK activity (CL2; Rho range 0.41–0.71). Individual BL cytokine levels were significantly associated with DAS28CRP, with unique biomarkers specific to various subcomponents of the score. Eleven biomarkers were associated with DAS28CRP, while 5, 3, and 2 were associated with CDAI, SJC28, and TJC28, respectively. The magnitude of FIL-associated treatment effects was time- and dose-dependent. Significant biomarker changes from BL were observed in FIL pts, relative to PBO+MTX pts. FIL100mg+MTX led to a significant change in 8 biomarkers by either 4 or 12 wks of treatment; FIL200mg+MTX significantly changed these and an additional 4 biomarkers by either time point. The greatest effect of FIL200mg+MTX was at 12 wks for CXCL13 (-38.4%) and IL6 (-53.7%). All treatment arms led to significant reductions in TNFα relative to PBO+MTX. FIL200mg+MTX treatment led to larger reductions of TNFα than ADA+MTX treatment at both wk4 (-24.7% vs -17.9%) and wk12 (-20.5% vs -12.2%), although the differences were not statistically significant.FIL and ADA caused differential patterns of cytokine response at either wks 4 or 12. Of 12 biomarkers with a significant FIL200mg+MTX treatment effect, there was a significantly larger reduction in TNFSF13B and CTX1 relative to ADA+MTX at 12 wks. Of 8 biomarkers with FIL100mg+MTX effects, only 2 (CXCL10 at wk 4; CXCL13 at wks 4 and 12) had significant differences from ADA+MTX. Relative either to FIL200mg+MTX or FIL100mg+MTX, and despite the same direction of effect, ADA+MTX led to a significantly larger reduction in CCL2, CXCL10, CCL4, and CXCL13.Conclusion:Compared with PBO, 12 wks of FIL treatment significantly reduced cytokines associated with JAK activity1, bone biology2, inflammation2, and immune cell migration2in MTX-IR pts. The effects were largely FIL dose-dependent; most cytokines exhibited similar effects regardless of treatment arms, but differential changes between FIL+MTX and ADA+MTX were observed, supportive of the different mechanisms of action of these therapies.References:[1]Majoros A, et al. Front Immunol. 2017;8:29[2]Brennan F, and McInnes I. J Clin Invest. 2008;118:3537-45Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc.

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