scholarly journals Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joseph A. C. Delaney ◽  
Nels C. Olson ◽  
Colleen M. Sitlani ◽  
Alison E. Fohner ◽  
Sally A. Huber ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Natural Killer Cells ◽  
Systolic Blood Pressure ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Average Systolic Blood Pressure ◽  
Immune Cell Subsets ◽  
Classical Monocytes

Abstract Background Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). Methods We assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level. Results The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16−) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure. Conclusion These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

scholarly journals The endometrial immune environment of women with endometriosis

2019 ◽  
Vol 25 (5) ◽  
pp. 565-592 ◽  
Author(s):  
Júlia Vallvé-Juanico ◽  
Sahar Houshdaran ◽  
Linda C Giudice
Keyword(s):  
T Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Reproductive Age ◽  
Cycle Phase ◽  
Cell Populations ◽  
Killer Cells

Abstract BACKGROUND Endometriosis, a common oestrogen-dependent inflammatory disorder in women of reproductive age, is characterized by endometrial-like tissue outside its normal location in the uterus, which causes pelvic scarring, pain and infertility. While its pathogenesis is poorly understood, the immune system (systemically and locally in endometrium, pelvic endometriotic lesions and peritoneal fluid) is believed to play a central role in its aetiology, pathophysiology and associated morbidities of pain, infertility and poor pregnancy outcomes. However, immune cell populations within the endometrium of women with the disease have had incomplete phenotyping, thereby limiting insight into their roles in this disorder. OBJECTIVE AND RATIONALE The objective herein was to determine reproducible and consistent findings regarding specific immune cell populations and their abundance, steroid hormone responsiveness, functionality, activation states, and markers, locally and systemically in women with and without endometriosis. SEARCH METHODS A comprehensive English language PubMed, Medline and Google Scholar search was conducted with key search terms that included endometriosis, inflammation, human eutopic/ectopic endometrium, immune cells, immune population, immune system, macrophages, dendritic cells (DC), natural killer cells, mast cells, eosinophils, neutrophils, B cells and T cells. OUTCOMES In women with endometriosis compared to those without endometriosis, some endometrial immune cells display similar cycle-phase variation, whereas macrophages (Mø), immature DC and regulatory T cells behave differently. A pro-inflammatory Mø1 phenotype versus anti-inflammatory Mø2 phenotype predominates and natural killer cells display abnormal activity in endometrium of women with the disease. Conflicting data largely derive from small studies, variably defined hormonal milieu and different experimental approaches and technologies. WIDER IMPLICATIONS Phenotyping immune cell subtypes is essential to determine the role of the endometrial immune niche in pregnancy and endometrial homeostasis normally and in women with poor reproductive history and can facilitate development of innovative diagnostics and therapeutics for associated symptoms and compromised reproductive outcomes.

Abstract 002: Circulating Levels of Natural Killer Cells and Monocyte Subsets Are Associated With Higher Systolic Blood Pressure: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Margaret F Doyle ◽  
Colleen M Sitlani ◽  
Nels C Olson ◽  
Sally A Huber ◽  
Alan L Landay ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Immune System ◽  
Systolic Blood Pressure ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Adaptive Immune ◽  
Circulating Levels

Introduction: Hypertension is a multifactorial process. Activation of the innate immune system and subsequent upregulation of adaptive immunity have been shown to promote hypertension in various mouse models Large scale human population studies examining the composition of the innate and adaptive immune system as it pertains to hypertension are lacking. Hypothesis: The composition of innate and adaptive immune cells are risk factors for increased systolic blood pressure (SBP). Methods: Using cells cryopreserved from the baseline exam, we measured 34 immune cell subsets from participants of the Multi-Ethnic Study of Atherosclerosis (MESA) (mean age 64 years, 53% male), sampled from a case-cohort study of myocardial infarction (n=1,200). SBP was assessed at baseline and at four follow-up exams over the succeeding ten years. Our approach to anti-hypertensive medication use was to add 10mmHG to SBP for treated participants. Associations between immune cell subpopulations and SBP were conducted using linear mixed models, with sampling weights to account for the sampling strategy and robust confidence intervals; immune cells were modeled per standard (SD) deviation higher value. We adjusted for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and log- transformed cytomegalovirus levels. Results: After adjustment for potential confounders, 5 of 34 immune cells subsets were significantly associated with mean levels of SBP. For each standard deviation increment higher immune cell proportion, natural killer (NK) cells, defined as CD3-CD56+CD16+, (1.9 mmHG; 95% CI: 0.8-2.9), classic monocytes, defined as CD14++CD16-, (-1.3 mmHG; 95% CI: -2.5 to -0.1) and non-classic monocytes, defined as CD14+CD16++, (1.4 mmHG; 95% CI: 0.3 to 2.6) had the strongest associations with SBP changes over 10-years of follow-up. Sensitivity analyses with principal components analysis were supportive of these findings. After using a Bonferroni corrected threshold to account for for multiple testing only NK remained significant. Conclusions: NK cells, classic monocytes and non-classic monocytes, all components of the innate immune system, were associated with higher levels of SBP over follow-up. The strongest association was with natural killer cells; in agreement with previous studies that showed circulating levels of interferon gamma and tumor necrosis factor alpha, the two main cytokines produced by NK cells, correlate with systolic blood pressure.

scholarly journals Immune cell composition in normal human kidneys

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun-Gyu Park ◽  
Myeongsu Na ◽  
Min-Gang Kim ◽  
Su Hwan Park ◽  
Hack June Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Kidney Diseases ◽  
Myeloid Cells ◽  
Human Kidney ◽  
Effector Memory ◽  
Immune Cell Subsets ◽  
Immunological Mechanisms ◽  
Normal Human

Abstract An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3+ T cells. Kidney CD4+ and CD8+ T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7− CD45RA− CD69−), and 48% ± 19% were kidney-resident cells (CCR7− CD45RA− CD69+). However, the proportions of human CD14+ and CD16+ myeloid cells were approximately 10% of total immune cells. A predominance of CD3+ T cells and a low proportion of CD14+ or CD68+ myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11blow F4/80high) were the most predominant subset (up to 50%) but the proportion of CD3+ T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.

scholarly journals Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T-cell subsets associated with disease progression

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Guohe Song ◽  
Yang Shi ◽  
Meiying Zhang ◽  
Shyamal Goswami ◽  
Saifullah Afridi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
T Cell Subsets ◽  
M2 Macrophage ◽  
Advanced Hcc ◽  
Immune Cell Subsets

AbstractDiverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune cell subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by diverse immune cell subsets that can transit among different states and mutually interact. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8+ T cells highly expressing XCL1 that correlated with better patient survival rates. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes, and evolution trajectory of effector CD8+ T cells from early-stage to advanced HCC were also identified. Our study provides insight into the immune microenvironment in HBV/HCV-related HCC and highlights novel macrophage and T-cell subsets that could be further exploited in future immunotherapy.

scholarly journals Key Immune Cell Subsets Are Dysregulated in Patients with Myelofibrosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5580-5580
Author(s):  
Marco Romano ◽  
Lucia Catani ◽  
Daria Sollazzo ◽  
Martina Barone ◽  
Margherita Perricone ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Th17 Cells ◽  
Immune Cell ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
High Rate ◽  
Healthy Controls ◽  
Immune Cell Subsets

Abstract Introduction: Myelofibrosis (MF) is a clonal disorder associated mainly with JAK2V617F and MPL mutations. Recently, a new mutation in the gene encoding calreticulin (CALR) was discovered in the majority of JAK2/MPL negative patients. MF is burdened by a high rate of potentially life-threatening infections. The issue of recurrent and opportunistic infections is increased after the introduction in clinical practice of JAK inhibitors with immunosuppressive activity. However, the role of crucial immune cell subsets is still poorly characterized. Here, we investigated the phenotype/function of selected immune cells in MF. Specifically, we focused on circulating regulatory (Tregs) and IL-17-producing T cells (Th17 cells), monocytes and dendritic cells (DCs). Monocyte-derived DCs were also characterized. Methods: We characterized circulating Th17 cells, Tregs, monocytes and DCs of 17 untreated MF patients and 8 healthy controls (HC) by flow cytometry. Th17 cells were identified as CD4+ CD161+ CD196+ cells while Tregs were enumerated as CD4+ CD25high CD127low T cells. We also tested the in vitro suppressive activity of circulating CD4+ CD25+ Tregs with a mixed leukocyte reaction assay. Two subpopulations of circulating DCs, myeloid CD11c+ and plasmacytoid CD123+cells, were enumerated as well. In addition, after immunomagnetic selection, we tested both phenotype of circulating monocytes and their capacity to differentiate into CD14-derived immature and mature DCs, using a specific cytokines cocktail. JAK2V617F and MPL mutations were detected with RT-PCR while the presence of CALR mutations were tested with Exon 9 Next Generation Sequencing assay. Results: JAK2V617F (11 cases), MPL (3 cases), and CARL (3 cases) mutations were detected. We found that circulating CD4+CD25highCD127low Tregs were reduced in MF patients as compared with healthy controls (p=0.043), although their suppressive ability was maintained. We also found a lower number of circulating Th17 cells (p=0.0026) in MF patients. This finding was particularly evident in JAK2V617F+(p=0.008) and CARL+(p=0.03) patients. Despite their number was in the normal range, circulating monocytes from MF patients showed reduced expression of the CD86 co-stimulatory molecule. Moreover, as compared with the normal counterparts, immature monocytes-derived DCs from patients maintained low CD14 expression without upregulating the CD80 co-stimulatory molecule expression (p=0.0063). Interestingly, at variance with plasmacytoid DCs, a reduced number of circulating myeloid DCs was observed in MF patients as compared with that of HC (p=0.01). Conclusions: Here we demonstrated that specific crucial subsets of immune cells show quantitative and/or qualitative abnormalities in MF patients. These findings may be useful to better understand the increased susceptibility of these patients to infections, since Th17 cells play a role in bacterial and fungal infections while myeloid DCs regulate Th1 activity. Of note, DCs inhibition might result in increased propensity to infections and compromised immune response to cancer.In addition, since monocytes are DC precursors, alterations in their differentiation pathway may contribute to develop defective immune responses. Disclosures Martinelli: NOVARTIS: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; PFIZER: Consultancy; ARIAD: Consultancy.

scholarly journals Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload–Driven Heart Failure Reveals Extent of Immune Activation

Circulation ◽  
2019 ◽  
Vol 140 (25) ◽  
pp. 2089-2107 ◽  
Author(s):  
Elisa Martini ◽  
Paolo Kunderfranco ◽  
Clelia Peano ◽  
Pierluigi Carullo ◽  
Marco Cremonesi ◽  
...  
Keyword(s):  
Heart Failure ◽  
T Cells ◽  
Mast Cells ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Immune Activation ◽  
Immune Cell ◽  
Pressure Overload ◽  
Cell Types

Background: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. Methods: Here, we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine nonischemic, pressure-overload heart failure model. By focusing our analysis on CD45 + cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multiparameter flow cytometry, immunohistochemistry, and tissue clarification immunofluorescence in mouse and human. Results: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells, dendritic cells, Natural Killer cells, neutrophils, and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whereas mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as oncostatin M in proinflammatory macrophages and PD-1 in regulatory T cells, that may help explain clinical findings such as the refractivity of patients with heart failure to anti–tumor necrosis factor therapy and cardiac toxicity during anti–PD-1 cancer immunotherapy, respectively. Conclusions: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, Natural Killer cells, and mast cells. This opens up the field of cardioimmunology to further investigation by using toolkits that have already been developed to study the aforementioned immune subsets. The subset-specific molecules that mediate their activation may thus become useful targets for the diagnostics or therapy of heart failure.

scholarly journals Lymphocytes and Trogocytosis-Mediated Signaling

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1478
Author(s):  
Jim Reed ◽  
Madison Reichelt ◽  
Scott A. Wetzel
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Intracellular Signaling ◽  
Immune Cell ◽  
Nk Cell ◽  
Γδ T Cells ◽  
Killer Cells ◽  
The Individual ◽  
The Impact

Trogocytosis is the intercellular transfer of membrane and membrane-associated molecules. This underappreciated process has been described in a variety of biological settings including neuronal remodeling, fertilization, viral and bacterial spread, and cancer, but has been most widely studied in cells of the immune system. Trogocytosis is performed by multiple immune cell types, including basophils, macrophages, dendritic cells, neutrophils, natural killer cells, B cells, γδ T cells, and CD4+ and CD8+ αβ T cells. Although not expressed endogenously, the presence of trogocytosed molecules on cells has the potential to significantly impact an immune response and the biology of the individual trogocytosis-positive cell. Many studies have focused on the ability of the trogocytosis-positive cells to interact with other immune cells and modulate the function of responders. Less understood and arguably equally important is the impact of these molecules on the individual trogocytosis-positive cell. Molecules that have been reported to be trogocytosed by cells include cognate ligands for receptors on the individual cell, such as activating NK cell ligands and MHC:peptide. These trogocytosed molecules have been shown to interact with receptors on the trogocytosis-positive cell and mediate intracellular signaling. In this review, we discuss the impact of this trogocytosis-mediated signaling on the biology of the individual trogocytosis-positive cell by focusing on natural killer cells and CD4+ T lymphocytes.

MO695THE ASSOCIATION OF CIRCULATING CD14++CD16+ MONOCYTES, NATURAL KILLER CELLS AND REGULATORY T CELLS SUBPOPULATIONS WITH CARDIOVASCULAR DISEASE IN A COHORT OF PERITONEAL DIALYSIS PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anila Duni ◽  
Olga Balafa ◽  
George Vartholomatos ◽  
Margarita Oikonomou ◽  
Paraskevi Tseke ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Peritoneal Dialysis ◽  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Normal Range ◽  
Immune Cell Subsets ◽  
Cell Subpopulations

Abstract Background and Aims Advanced chronic kidney disease (CKD) is characterized by elevated expression of the proinflammatory and pro-atherogenic CD14++CD16+ monocytes subset. The role of lymphocyte subpopulations including natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention. The role of immune cell subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim of this pilot study was to investigate potential correlations between blood levels of CD14++CD16+ monocytes, NK cells and Tregs with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in a cohort of PD patients. Method 29 stable PD patients (mean age 66.96 years ±14.5, 62% males) were enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active or chronic infections and a recent (< 3 months) cardiovascular event. Demographic, laboratory and bioimpedance measurements data (overhydration, extracellular and total body water and their ratios) were collected. The analysis of peripheral blood immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD patients the distribution of the immune cells was evaluated by FC at two time points: T0 (before initiation of PD - CKD stage G5) and T1 (after PD start). Results The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD patients had 527 ± 199 monocytes and 1731 ± 489 lymphocytes while mean percentage of CD14++CD16+ monocytes was 9.3 ±6.36% (normal range 2-8%), NK cells 16.6±10.3% (normal range 5-15%) and Tregs 2.1±1.76% (normal range 1-3%). There was no correlation of either of these cell subpopulations with age, PD vintage, inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration markers or comorbidities. Only increased NK cells were associated with the presence of HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels were strongly associated with the presence of edema (beta coef=13.7, p<0.001) and CAD (beta coef=7.1, p=0.046). At T0 mean percentage of CD14++CD16+ monocytes, NK cells and Tregs were 9.7 ±4.5%, 17.1 ±3.84% and 2.38± 1.26% respectively whereas at T1 mean percentage of CD14++CD16+ monocytes was 13.3% ±8.4, NK cells 19.8±6.47% and Tregs 1.5±0.6%. Paired t-test of cell subpopulations (T0 vs T1) showed that only the Tregs were significantly decreased (p =0.018), while the other subpopulations did not differ and remained increased. Conclusion Our study is the first to evaluate the potential association between specific immune cell subsets and cardiovascular disease in long-term PD patients. Increased NK cells levels directly correlate both with the presence of HF and CAD in PD patients. Longitudinal results suggest that CD14++CD16+ and NK cells remain increased after PD start, while Tregs decrease further. The state of pro-inflammation and immune deregulation appear to persist after initiating PD. Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients who are at the highest risk for complications and to guide interventions that may improve clinical outcomes.

Abstract 175: The Role of Axl in Accumulation of Immune Cells in Kidney and the Onset of Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sri Nagarjun Batchu ◽  
Angie Hughson ◽  
Janice Gerloff ◽  
Deborah J Fowell ◽  
Vyacheslav A Korshunov
Keyword(s):  
Blood Pressure ◽  
Immune Cells ◽  
Immune Cell ◽  
Kidney Injury ◽  
Wild Type ◽  
Protein Levels ◽  
Immune Cell Subsets ◽  
Early Increase ◽  
Salt Hypertension

Introduction: Gas6/Axl pathway contributes to elevation of blood pressure. Immune cells are implicated in initiation and maintenance of hypertension. In this study we aimed to investigate the role of Axl in immune cells on kidney injury and initiation of hypertension. Methods and Results: Deoxycorticosterone-acetate (DOCA; 75mg, 60days release) and salt hypertension was induced for 1wk or 6wks in four groups of Axl chimeras (n=4-5) that were generated by bone marrow (BM) transplant. Multi parameter flow cytometry was used to quantify five major immune cell subsets in digested kidneys from Axl chimeras. Systolic blood pressure (SBP) increased by 30mmHg in Axl+/+ →Axl+/+, Axl-/- →Axl-/- and Axl+/+ →Axl-/- mice after 1wk of DOCA-salt. However, chimeras that lack Axl in the BM cells (Axl-/- →Axl+/+) showed reduction in early increase in SBP (16+2mmHg). We observed a significant decrease in urine protein levels in Axl-/- →Axl+/+ (0.3+0.1μg/μl) compared to other Axl chimeras (∼0.7μg/μl) after 1wk of DOCA-salt. Kidney glomeruli areas were reduced in Axl-/- →Axl+/+ (4,143+229μm 2 ) compared to other Axl chimeras (∼6,000μm 2 ) after 6wks of DOCA-salt. Kidneys from Axl-/- →Axl-/- showed an increase in total leukocytes (8 vs. 4%), B cells (29 vs. 12%) and decrease in monocytes/macrophages (16 vs. 22%) and dendritic cells (5 vs. 10%) compared to Axl+/+ →Axl+/+. Moreover, Axl-/- →Axl+/+ showed further increase in leukocytes (17%), B (39%) and dendritic (13%) cells in kidneys compared to other Axl chimeras. In addition a small percentage of wild type T cells was increased in the kidneys from Axl-/- →Axl+/+ chimeras. Conclusions: These findings suggest that Axl expression in BM-derived cells is critical for kidney injury in DOCA-salt hypertension. Axl-dependent pathways regulate immune cell populations in the kidneys during initiation of hypertension. This study was supported by HL105623 grant (VAK)

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