scholarly journals Single-Dose SARS-CoV-2 Vaccination With BNT162b2 and AZD1222 Induce Disparate Th1 Responses and IgA Production

2021 ◽  
Author(s):  
Michael Müller ◽  
Johann Volzke ◽  
Behnam Subin ◽  
Silke Müller ◽  
Martina Sombetzki ◽  
...  
Keyword(s):  
T Cells ◽  
Single Dose ◽  
Immune Cell ◽  
Antigen Delivery ◽  
Vaccination Programs ◽  
Immune Priming ◽  
Specific Effector ◽  
Iga Production ◽  
Antibody Dynamics ◽  
Cell Effector

AbstractWhile vaccination programs against SARS-CoV-2 are globally ongoing, disparate strategies for the deployment of spike antigen show varying effectiveness. In order to explore this phenomenon, we sought to compare the early immune responses against AZD1222 and BNT162b2. SARS-CoV-2 seronegative participants received a single dose of either vaccine and were analyzed for immune cell, effector T cell and antibody dynamics. AZD1222 induced transient leukopenia and major changes among innate and adaptive subpopulations. Both vaccines induced spike protein specific effector T cells which were dominated by Th1 responses following AZD1222 vaccination. A significant reduction of anti-inflammatory T cells upon re-stimulation was also restricted to AZD1222 vaccinees. While IgM and IgG were the dominant isotypes elicited by AZD1222, BNT162b2 led to a significant production of IgG and IgA. Our results suggest that the strategy for spike antigen delivery impacts on how and to what extent immune priming against the main SARS-CoV-2 antigen proceeds.

scholarly journals Metabolic and Epigenomic Regulation of Th17/Treg Balance by the Polyamine Pathway

2020 ◽  
Author(s):  
Chao Wang ◽  
Allon Wagner ◽  
Johannes Fessler ◽  
Julian Avila-Pacheco ◽  
Jim Karminski ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Metabolic Flux ◽  
Cell Function ◽  
Immune Cell ◽  
Disease Model ◽  
Epigenomic Regulation ◽  
Dramatic Shift ◽  
Cell Effector

ABSTRACTCellular metabolism can orchestrate immune cell function. We previously demonstrated that lipid biosynthesis represents one such gatekeeper to Th17 cell functional state. Utilizing Compass, a transcriptome-based algorithm for prediction of metabolic flux, we constructed a comprehensive metabolic circuitry for Th17 cell function and identified the polyamine pathway as a candidate metabolic node, the flux of which regulates the inflammatory function of T cells. Testing this prediction, we found that expression and activities of enzymes of the polyamine pathway were enhanced in pathogenic Th17 cells and suppressed in regulatory T cells. Perturbation of the polyamine pathway in Th17 cells suppressed canonical Th17 cell cytokines and promoted the expression of Foxp3, accompanied by dramatic shift in transcriptome and epigenome, transitioning Th17 cells into a Treg-like state. Genetic and chemical perturbation of the polyamine pathway resulted in attenuation of tissue inflammation in an autoimmune disease model of central nervous system, with changes in T cell effector phenotype.

scholarly journals SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

2021 ◽  
Author(s):  
Lu Yuan ◽  
Xixi Wu ◽  
Longshan Zhang ◽  
Mi Yang ◽  
Xiaoqing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Expression Profile ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Regulatory Pathways ◽  
Chronic Lung Diseases ◽  
Potential Biomarker

AbstractPulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

747 Evaluation of immune microenvironment of primary lung cancer and synchronous liver metastasis with multispectral imaging system

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A795-A795
Author(s):  
Hyeonbin Cho ◽  
Jae-Hwan Kim ◽  
Ji-Hyun Kim
Keyword(s):  
T Cells ◽  
Liver Metastasis ◽  
Multispectral Imaging ◽  
Immune Cell ◽  
Imaging System ◽  
Cytotoxic T Cells ◽  
Primary Lung Cancer ◽  
Helper T Cells ◽  
Synchronous Liver Metastasis ◽  
Immune Microenvironment

BackgroundCancer immunotherapy (CIT) has substantially improved the survival of cancer patients. However, according to recent studies, liver metastasis was reported to predict worse outcomes for CIT. The main objective of the study is to evaluate the differences in the immune microenvironment (IME) between the primary lung cancer (PL) and synchronous liver metastasis (LM) using a multispectral imaging system.MethodsSix immune markers (CD4, CD8, CTLA-4, granzyme B (GZB), Foxp3 and PD-L1) were analyzed using a multiplex IHC system and inForm program (Akoya) on paired lung-liver samples of 10 patients. Cells were categorized into tumor nest and stroma, and cell counts per unit area were measured for comparison.ResultsThe number of tumor-infiltrating cytotoxic T cells (TIL) in PL (262.5 cells/mm2) was higher than that of LM (113.3 cells/mm2). Additionally, the ratio between the number of TIL and non-TIL was greater in PL (0.31) compared to that of LM (0.26). A similar trend appeared for Helper T cells and regulatory T cells (Treg), as PL consisted of higher numbers of T cells (791.8 Helper T cells/mm2, 195.7 Treg/mm2) than LM (626.3 Helper T cells/mm2, 121.3 Treg/mm2). However, cytotoxic T cells exhibiting GZB+ and CTLA-4- were fewer in PL (140.2 cells/mm2) than in LM (203.3 cells/mm2), and the ratio is 0.69. The mean number of GZB+ TIL in PL (32.5 cells/mm2) was lower than in LM (35.3 cells/mm2), and their proportions among total TIL counts were 0.12 and 0.31, respectively. In PL, GZB+: GZB- ratio is 0.16 while the ratio is 1.91 for LM. A fewer number of TILs exhibiting GZB suggests that PL has lower efficiency in immune response than LM. Another crucial checkpoint receptor that inhibits immune response, CTLA-4, was more prevalent in PL, with CTLA-4+: CTLA-4- ratio in Treg being 0.36 in PL, compared to 0.11 in LM. The tumor proportion score (TPS) of PD-L1 was higher in PL than LM (40.0 vs. 6.6).ConclusionsIn our study, we showed the differences in the numbers of TIL or regulatory T cells and expressions of immune checkpoint receptors (PD-L1, CTLA-4), which significantly influence outcomes for CIT. The study is ongoing to confirm different IME between the PL and LM groups in a larger tumor cohort.ReferencesPeng, Jianhong, et al., Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy. Cancers 2019 Dec; 11(12): 1922. https://doi.org/10.3390/cancers11121922Tumeh, Paul C., et al., Liver Metastasis and treatment outcome with Anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res 2017 May; 5(5): 417–424. doi: 10.1158/2326-6066.CIR-16-0325Parra, E.R., Immune Cell Profiling in Cancer Using Multiplex Immunofluorescence and Digital Analysis Approaches; Streckfus, C.F., Ed.; IntechOpen: London, UK, 2018; pp. 1–13. doi: 10.5772/intechopen.80380Ribas, A., Hu-Lieskovan, S., What does PD-L1 positive or negative mean?. The Journal of Experimental Medicine 2016;213(13):2835–2840. https://doi.org/10.1084/jem.20161462

scholarly journals Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2096
Author(s):  
Celina L. Szanto ◽  
Annelisa M. Cornel ◽  
Sara M. Tamminga ◽  
Eveline M. Delemarre ◽  
Coco C. H. de Koning ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Nk Cells ◽  
Immune Cell ◽  
High Dose Chemotherapy ◽  
Immune Monitoring ◽  
High Dose ◽  
Effector Cells ◽  
Gm Csf ◽  
Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

scholarly journals Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander J. Dwyer ◽  
Jacob M. Ritz ◽  
Jason S. Mitchell ◽  
Tijana Martinov ◽  
Mohannad Alkhatib ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Convex Hull ◽  
Pancreatic Islets ◽  
Immune Cell ◽  
Nod Mice ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Analytical Strategy ◽  
Islet Mass

AbstractThe notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.

scholarly journals Structures of mouse and human GITR–GITRL complexes reveal unique TNF superfamily interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Wang ◽  
Bryant Chau ◽  
Sean M. West ◽  
Christopher R. Kimberlin ◽  
Fei Cao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Signaling ◽  
Tumor Necrosis ◽  
Immune Cell ◽  
Linear Chain ◽  
Tumor Necrosis Factor Receptor ◽  
Higher Order ◽  
Membrane Structures ◽  
Receptor Interface

AbstractGlucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.

scholarly journals 602 STING agonist-based treatment promotes vascular normalization and tertiary lymphoid structure formation in the therapeutic melanoma microenvironment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A637-A637
Author(s):  
Manoj Chelvanambi ◽  
Ronald Fecek ◽  
Jennifer Taylor ◽  
Walter Storkus
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
In Vitro Assays ◽  
Type I ◽  
Vascular Normalization ◽  
S 100 ◽  
Transcriptional Changes

BackgroundThe degree of immune infiltration in tumors, especially CD8+ T cells, greatly impacts patient disease course and response to interventional immunotherapy. Hence, enhancement of TIL prevalence is a preferred clinical endpoint, one that may be achieved via administration of agents that normalize the tumor vasculature (VN) leading to improved immune cell recruitment and/or that induce the development of local tertiary lymphoid structures (TLS) within the tumor microenvironment (TME).MethodsLow-dose STING agonist ADU S-100 (5 μg/mouse) was delivered intratumorally to established s.c. B16.F10 melanomas on days 10, 14 and 17 post-tumor inoculation under an IACUC-approved protocol. Treated and control, untreated tumors were isolated at various time points to assess transcriptional changes associated with VN and TLS formation via qPCR, with corollary immune cell composition changes determined using flow cytometry and immunofluorescence microscopy. In vitro assays were performed on CD11c+ BMDCs treated with 2.5 μg/mL ADU S-100 (vs PBS control) and associated transcriptional changes analyzed via qPCR or profiled using DNA microarrays. For TCRβ-CDR3 analyses, CDR3 was sequenced from gDNA isolated from enzymatically digested tumors and splenocytes.ResultsWe report that activation of STING within the TME leads to slowed melanoma growth in association with increased production of angiostatic factors including Tnfsf15 (Vegi), Cxcl10 and Angpt1, and TLS inducing factors including Ccl19, Ccl21, Lta, Ltb and Tnfsf14 (Light). Therapeutic responses from intratumoral STING activation were characterized by increased vascular normalization (VN), enhanced tumor infiltration by CD8+ T cells and CD11c+ DCs and local TLS neo-genesis, all of which were dependent on host expression of STING. Consistent with a central role for DC in TLS formation, ex vivo ADU S-100-activated mCD11c+ DCs also exhibited upregulated expression of TLS promoting factors including lymphotoxin-α (LTA), IL-36, inflammatory chemokines and type I interferons. TLS formation was associated with the development of a therapeutic TIL TCR repertoire enriched in T cell clonotypes uniquely detected within the tumor but not the peripheral circulation in support or local T cell cross-priming within the TME.ConclusionsOur data support the premise that i.t. delivery of STING agonist promotes a pro-inflammatory TME in support of VN and TLS formation, leading to the local expansion of unique TIL repertoire in association with superior anti-melanoma efficacy.

scholarly journals Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34+ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Marcus Bauer ◽  
Christoforos Vaxevanis ◽  
Haifa Kathrin Al-Ali ◽  
Nadja Jaekel ◽  
Christin Le Hoa Naumann ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Multispectral Imaging ◽  
Immune Cell ◽  
Genetic Alterations ◽  
Spatial Proximity ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34+ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8+ and FOXP3+ T cells and only single MUM1p+ B/plasma cells were detected in an area of ≤10 μm to CD34+ HSPC. Conclusions: CD8+ and FOXP3+ T cells are regularly seen in the 10 μm area around CD34+ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34+ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.

scholarly journals AB0128 CXCL5 DAMPENS INFLAMMATION IN THE PRE-CLINICAL MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS VIA THE ORCHESTRAL EFFECT OF REGULATING NEUTROPHIL TRAFFICKING AND SUPPRESSING HELPER T CELL-MEDIATED IMMUNE RESPONSE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1365.2-1365
Author(s):  
X. Fan ◽  
D. Guo ◽  
C. T. Ng ◽  
A. Law ◽  
Z. Y. Poon ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Systemic Lupus ◽  
Helper T Cell ◽  
Clinical Model ◽  
Cell Mediated Immune Response

Background:Patients with systemic lupus erythematosus (SLE) suffer from severe morbidity and mortality1-4, either from the disease itself or from side effects of immunosuppression5. Discovery of novel effective therapies with less toxicity is an urgent need.Objectives:The aim of this study is to elucidate the therapeutic potential and working mechanism of cytokine CXCL5 in lupus mice.Methods:Treatment with CXCL5, bone marrow (BM)-MSCs, standard of care (SOC) with combination of methylprednisolone and cyclophosphamide was given to 16-week-old Faslprmice. Mice were monitored for 10 weeks. Splenic immune cell subsets were measured by flow cytometry. Circulating cytokine and immunoglobulin were detected by Luminex technology. Renal function was evaluated by urinary spot albumin creatinine ratio. In situ renal immune cell infiltration and complement 3 deposition were detected by Haematoxylin and Eosin (H&E) staining and immunohistochemistry.Results:CXCL5 demonstrated consistent and potent immunosuppressive capacity in suppressing SLE with reduced autoantibody secretion, lymphoproliferation and preserved kidney function. With further exploration, we proved that CXCL5 reduced the proliferation of helper T cells (TH1 and TH2) in thein vitrofunctional assay. When we administrated CXCL5 to lupus mice, it promoted the proliferation of regulatory T cells and reduced the proliferation of TH17 cells, macrophages and neutrophils. Multiple proinflammatory cytokines including IL-2, IL-6, IL-12, IL-17A, KC/CXCL1, MIP-1β/CCL4 and TNF-α were also reduced. When combined with SOC, CXCL5 boosted its therapeutic effect and reduced the relevant indices of disease activity. When we correlated the effect of four different treatment groups (CXCL5, BM-MSCs, SOC, and CXCL5 plus SOC) on mice survival and target cell changes, we found that TH17 cells were the key effector cells involved in the pathogenesis of SLE.Conclusion:These findings demonstrated that CXCL5 dampens inflammation in the pre-clinical model of systemic lupus erythematosus via the orchestral effect of regulating neutrophil trafficking and suppressing helper T cell-mediated immune response. Administrating exogenous CXCL5 might be an attractive option to treat patients with lupus.References:[1]Ji S, Guo Q, Han Y, Tan G, Luo Y, Zeng F. Mesenchymal stem cell transplantation inhibits abnormal activation of Akt/GSK3beta signaling pathway in T cells from systemic lupus erythematosus mice.Cell Physiol Biochem.2012;29(5-6):705-712.[2]Peng SL. Altered T and B lymphocyte signaling pathways in lupus.Autoimmun Rev.2009;8(3):179-183.[3]Ferucci ED, Johnston JM, Gaddy JR, et al. Prevalence and incidence of systemic lupus erythematosus in a population-based registry of American Indian and Alaska Native people, 2007-2009.Arthritis Rheumatol.2014;66(9):2494-2502.[4]Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality.Arthritis Care Res (Hoboken).2012;64(2):159-168.[5]Sattwika PD, Mustafa R, Paramaiswari A, Herningtyas EH. Stem cells for lupus nephritis: a concise review of current knowledge.Lupus.2018;27(12):1881-1897.Acknowledgments:The work was supported by SMART II Centre Grant (NMRC/CG/M011/2017_SGH) and SingHealth Foundation (SHF/FG638P/2016).Disclosure of Interests:None declared

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