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1. Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients

Author

Lokken, Erica M., Taylor, G. Gray, Huebner, Emily M., Vanderhoeven, Jeroen, Hendrickson, Sarah, Coler, Brahm, Sheng, Jessica S., Walker, Christie L., McCartney, Stephen A., Kretzer, Nicole M., Resnick, Rebecca, Kachikis, Alisa, Barnhart, Nena, Schulte, Vera, Bergam, Brittany, Ma, Kimberly K., Albright, Catherine, Larios, Valerie, Kelley, Lori, Larios, Victoria, Emhoff, Sharilyn, Rah, Jasmine, Retzlaff, Kristin, Thomas, Chad, Paek, Bettina W., Hsu, Rita J., Erickson, Anne, Chang, Andrew, Mitchell, Timothy, Hwang, Joseph K., Gourley, Rebecca, Erickson, Stephen, Delaney, Shani, Kline, Carolyn R., Archabald, Karen, Blain, Michela, LaCourse, Sylvia M., and Adams Waldorf, Kristina M.

Published
2021
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2. Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State

Author

Lokken, Erica M., Huebner, Emily M., Taylor, G. Gray, Hendrickson, Sarah, Vanderhoeven, Jeroen, Kachikis, Alisa, Coler, Brahm, Walker, Christie L., Sheng, Jessica S., al-Haddad, Benjamin J.S., McCartney, Stephen A., Kretzer, Nicole M., Resnick, Rebecca, Barnhart, Nena, Schulte, Vera, Bergam, Brittany, Ma, Kimberly K., Albright, Catherine, Larios, Valerie, Kelley, Lori, Larios, Victoria, Emhoff, Sharilyn, Rah, Jasmine, Retzlaff, Kristin, Thomas, Chad, Paek, Bettina W., Hsu, Rita J., Erickson, Anne, Chang, Andrew, Mitchell, Timothy, Hwang, Joseph K., Erickson, Stephen, Delaney, Shani, Archabald, Karen, Kline, Carolyn R., LaCourse, Sylvia M., and Adams Waldorf, Kristina M.

Published
2021
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5. Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State

Author

Lokken, Erica M., Walker, Christie L., Delaney, Shani, Kachikis, Alisa, Kretzer, Nicole M., Erickson, Anne, Resnick, Rebecca, Vanderhoeven, Jeroen, Hwang, Joseph K., Barnhart, Nena, Rah, Jasmine, McCartney, Stephen A., Ma, Kimberly K., Huebner, Emily M., Thomas, Chad, Sheng, Jessica S., Paek, Bettina W., Retzlaff, Kristin, Kline, Carolyn R., Munson, Jeff, Blain, Michela, LaCourse, Sylvia M., Deutsch, Gail, and Adams Waldorf, Kristina M.

Published
2020
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6. Supplementary Data from The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain

Author

Bowman-Kirigin, Jay A., primary, Desai, Rupen, primary, Saunders, Brian T., primary, Wang, Anthony Z., primary, Schaettler, Maximilian O., primary, Liu, Connor J., primary, Livingstone, Alexandra J., primary, Kobayashi, Dale K., primary, Durai, Vivek, primary, Kretzer, Nicole M., primary, Zipfel, Gregory J., primary, Leuthardt, Eric C., primary, Osbun, Joshua W., primary, Chicoine, Michael R., primary, Kim, Albert H., primary, Murphy, Kenneth M., primary, Johanns, Tanner M., primary, Zinselmeyer, Bernd H., primary, and Dunn, Gavin P., primary

Published
2023
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7. Data from The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain

Author

Bowman-Kirigin, Jay A., primary, Desai, Rupen, primary, Saunders, Brian T., primary, Wang, Anthony Z., primary, Schaettler, Maximilian O., primary, Liu, Connor J., primary, Livingstone, Alexandra J., primary, Kobayashi, Dale K., primary, Durai, Vivek, primary, Kretzer, Nicole M., primary, Zipfel, Gregory J., primary, Leuthardt, Eric C., primary, Osbun, Joshua W., primary, Chicoine, Michael R., primary, Kim, Albert H., primary, Murphy, Kenneth M., primary, Johanns, Tanner M., primary, Zinselmeyer, Bernd H., primary, and Dunn, Gavin P., primary

Published
2023
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12. The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain

Author

Bowman-Kirigin, Jay A., primary, Desai, Rupen, additional, Saunders, Brian T., additional, Wang, Anthony Z., additional, Schaettler, Maximilian O., additional, Liu, Connor J., additional, Livingstone, Alexandra J., additional, Kobayashi, Dale K., additional, Durai, Vivek, additional, Kretzer, Nicole M., additional, Zipfel, Gregory J., additional, Leuthardt, Eric C., additional, Osbun, Joshua W., additional, Chicoine, Michael R., additional, Kim, Albert H., additional, Murphy, Kenneth M., additional, Johanns, Tanner M., additional, Zinselmeyer, Bernd H., additional, and Dunn, Gavin P., additional

Published
2022
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13. L-Myc expression by dendritic cells is required for optimal T-cell priming

Author

Wumesh, K.C., Satpathy, Ansuman T., Rapaport, Aaron S., Briseno, Carlos G., Wu, Xiaodi, Albring, Jorn C., Russler-Germain, Emilie V., Kretzer, Nicole M., Durai, Vivek, Persaud, Stephen P., Edelson, Brian T., Loschko, Jakob, Cella, Marina, Allen, Paul M., Nussenzweig, Michel C., Colonna, Marco, Sleckman, Barry P., Murphy, Theresa L., and Murphy, Kenneth M.

Subjects
Research, Genetic aspects, Cytological research, Dendritic cells -- Genetic aspects, Gene expression -- Research, T cells -- Genetic aspects, Cell research
Abstract

The transcription factors c-Myc and N-Myc--encoded by Myc and Mycn, respectively--regulate cellular growth (1) and are required for embryonic development (2,3). A third paralogue, Mycl1, is dispensable for normal embryonic [...]

Published
2014

15. The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive anti-tumor immunity in the brain

Author

Bowman-Kirigin, Jay A., primary, Saunders, Brian T., additional, Desai, Rupen, additional, Wang, Anthony Z., additional, Schaettler, Max O., additional, Liu, Connor J., additional, Livingstone, Alexandra J., additional, Kobayashi, Dale K., additional, Durai, Vivek, additional, Kretzer, Nicole M., additional, Zipfel, Gregory J., additional, Leuthardt, Eric C., additional, Osbun, Joshua W., additional, Chicoine, Michael R., additional, Kim, Albert H., additional, Murphy, Kenneth M., additional, Johanns, Tanner M., additional, Zinselmeyer, Bernd H., additional, and Dunn, Gavin P., additional

Published
2021
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16. Compensatory dendritic cell development mediated by BATF–IRF interactions

Author

Tussiwand, Roxane, Lee, Wan-Ling, Murphy, Theresa L., Mashayekhi, Mona, KC, Wumesh, Albring, Jörn C., Satpathy, Ansuman T., Rotondo, Jeffrey A., Edelson, Brian T., Kretzer, Nicole M., Wu, Xiaodi, Weiss, Leslie A., Glasmacher, Elke, Li, Peng, Liao, Wei, Behnke, Michael, Lam, Samuel S. K., Aurthur, Cora T., Leonard, Warren J., Singh, Harinder, Stallings, Christina L., Sibley, L. David, Schreiber, Robert D., and Murphy, Kenneth M.

Published
2012
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17. L-Myc expression by dendritic cells is required for optimal T-cell priming

Author

KC, Wumesh, Satpathy, Ansuman T., Rapaport, Aaron S., Briseño, Carlos G., Wu, Xiaodi, Albring, Jörn C., Russler-Germain, Emilie V., Kretzer, Nicole M., Durai, Vivek, Persaud, Stephen P., Edelson, Brian T., Loschko, Jakob, Cella, Marina, Allen, Paul M., Nussenzweig, Michel C., Colonna, Marco, Sleckman, Barry P., Murphy, Theresa L., and Murphy, Kenneth M.

Published
2014
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18. Higher SARS-CoV-2 Infection Rate in Pregnant Patients

Author

LOKKEN, Erica M., TAYLOR, G. Gray, HUEBNER, Emily M., VANDERHOEVEN, Jeroen, HENDRICKSON, Sarah, COLER, Brahm, SHENG, Jessica S., WALKER, Christie L., MCCARTNEY, Stephen A., KRETZER, Nicole M., RESNICK, Rebecca, KACHIKIS, Alisa, BARNHART, Nena, SCHULTE, Vera, BERGAM, Brittany, K, Kimberly, ALBRIGHT, Catherine, LARIOS, Valerie, KELLEY, Lori, LARIOS, Victoria, EMHOFF, Sharilyn, RAH, Jasmine, RETZLAFF, Kristin, THOMAS, Chad, PAEK, Bettina W., HSU, Rita J., ERICKSON, Anne, CHANG, Andrew, MITCHELL, Timothy, HWANG, Joseph K., GOURLEY, Rebecca, ERICKSON, Stephen, DELANEY, Shani, KLINE, Carolyn R., ARCHABALD, Karen, BLAIN, Michela, LACOURSE, Sylvia M., and ADAMS WALDORF, Kristina M.

Subjects
Alaskan Native, Adult, Washington, Washington State, SARS-CoV-2, Original Research: Obstetrics, Racial Groups, coronavirus, Hispanic, COVID-19, Severity of Illness Index, Cohort Studies, fetus, Pacific Islander, Young Adult, ethnic disparity, Black, Pregnancy, American Indian, Humans, Female, Pregnancy Complications, Infectious, Retrospective Studies
Abstract

During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood.This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State.Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State.A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%).The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Published
2021

19. Clinical Characteristics of 46 Pregnant Women with a SARS-CoV-2 Infection in Washington State

Author

Lokken, Erica M., Walker, Christie L., Delaney, Shani, Kachikis, Alisa, Kretzer, Nicole M., Erickson, Anne, Resnick, Rebecca, Vanderhoeven, Jeroen, Hwang, Joseph K., Barnhart, Nena, Rah, Jasmine, Mccartney, Stephen A., Ma, Kimberly K., Huebner, Emily M., Thomas, Chad, Sheng, Jessica S., Paek, Bettina W., Retzlaff, Kristin, Kline, Carolyn R., Munson, Jeff, Blain, Michela, Lacourse, Sylvia M., Deutsch, Gail, and Adams Waldorf, Kristina

Subjects
obesity, SARS-CoV-2, coronavirus, preterm birth, asthma, Article, infection, maternal morbidity, respiratory insufficiency, overweight, stillbirth, pregnancy, fetal death, Covid-19
Abstract

Background The impact of the coronavirus disease 2019 (Covid-19) on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease. Objective To describe maternal disease and obstetrical outcomes associated with Covid-19 disease in pregnancy to rapidly inform clinical care. Study Design Retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection from six hospital systems in Washington State between January 21, 2020 and April 17, 2020. Demographics, medical and obstetric history, and Covid-19 encounter data were abstracted from medical records. Results A total of 46 pregnant patients with a SARS-CoV-2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a SARS-CoV-2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5%, n=20 and 50.0%, n=23, respectively). Symptoms resolved in a median of 24 days (interquartile range 13-37). Seven women were hospitalized (16%) including one admitted to the intensive care unit. Six cases (15%) were categorized as severe Covid-19 disease with nearly all patients being either overweight or obese prior to pregnancy, asthma or other co-morbidities. Eight deliveries occurred during the study period, including a preterm birth at 33 weeks to improve pulmonary status in a woman with Class III obesity. One stillbirth occurred of unknown etiology. Conclusions Nearly 15% of pregnant patients developed severe Covid-19, which occurred primarily in overweight or obese women with underlying conditions. Obesity and Covid-19 may synergistically increase risk for a medically-indicated preterm birth to improve maternal pulmonary status in late pregnancy. Collectively, these findings support categorizing pregnant patients as a higher risk group, particularly for those with chronic co-morbidities.

Published
2020

21. Low Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Pregnant and Postpartum Patients With Universal Screening in Seattle, Washington

Author

LaCourse, Sylvia M, primary, Kachikis, Alisa, additional, Blain, Michela, additional, Simmons, LaVone E, additional, Mays, James A, additional, Pattison, Amber D, additional, Salerno, Carol C, additional, McCartney, Stephen A, additional, Kretzer, Nicole M, additional, Resnick, Rebecca, additional, Shay, Rosemary L, additional, Savitsky, Leah M, additional, Curtin, Anna C, additional, Huebner, Emily M, additional, Ma, Kimberly K, additional, Delaney, Shani, additional, Delgado, Carlos, additional, Schippers, Adrienne, additional, Munson, Jeff, additional, Pottinger, Paul S, additional, Cohen, Seth, additional, Neme, Santiago, additional, Bourassa, Lori, additional, Bryan, Andrew, additional, Greninger, Alex, additional, Jerome, Keith R, additional, Roxby, Alison C, additional, Lokken, Erica, additional, Cheng, Edith, additional, Adams Waldorf, Kristina M, additional, and Hitti, Jane, additional

Published
2020
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22. MicroRNA Signature of Epithelial-Mesenchymal Transition in Group B Streptococcal Infection of the Placental Chorioamniotic Membranes

Author

Weed, Samantha, primary, Armistead, Blair, additional, Coleman, Michelle, additional, Liggit, H Denny, additional, Johnson, Brian, additional, Tsai, Jesse, additional, Beyer, Richard P, additional, Bammler, Theodor K, additional, Kretzer, Nicole M, additional, Parker, Ed, additional, Vanderhoeven, Jeroen P, additional, Bierle, Craig J, additional, Rajagopal, Lakshmi, additional, and Adams Waldorf, Kristina M, additional

Published
2020
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23. A Broad Spectrum Chemokine Inhibitor Prevents Preterm Labor but Not Microbial Invasion of the Amniotic Cavity or Neonatal Morbidity in a Non-human Primate Model

Author

Coleman, Michelle, primary, Orvis, Austyn, additional, Wu, Tsung-Yen, additional, Dacanay, Matthew, additional, Merillat, Sean, additional, Ogle, Jason, additional, Baldessari, Audrey, additional, Kretzer, Nicole M., additional, Munson, Jeff, additional, Boros-Rausch, Adam J., additional, Shynlova, Oksana, additional, Lye, Stephen, additional, Rajagopal, Lakshmi, additional, and Adams Waldorf, Kristina M., additional

Published
2020
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25. Low Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Pregnant and Postpartum Patients With Universal Screening in Seattle, Washington.

Author

LaCourse, Sylvia M, Kachikis, Alisa, Blain, Michela, Simmons, LaVone E, Mays, James A, Pattison, Amber D, Salerno, Carol C, McCartney, Stephen A, Kretzer, Nicole M, Resnick, Rebecca, Shay, Rosemary L, Savitsky, Leah M, Curtin, Anna C, Huebner, Emily M, Ma, Kimberly K, Delaney, Shani, Delgado, Carlos, Schippers, Adrienne, Munson, Jeff, and Pottinger, Paul S

Subjects
COVID-19, ACQUISITION of data methodology, MEDICAL screening, RETROSPECTIVE studies, PUERPERIUM, MEDICAL records, DESCRIPTIVE statistics, DISEASE prevalence, COVID-19 testing, PREGNANCY
Abstract

We found low prevalence of SARS-CoV-2 (2.7% [5/188]) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted screening (22.2% [4/18]) and universal approaches (19.1% [8/42]). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative. [ABSTRACT FROM AUTHOR]

Published
2021
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27. Opposing Roles of Dendritic Cell Subsets in Experimental GN

Author

Brahler, Sebastian, Zinselmeyer, Bernd H., Raju, Saravanan, Nitschke, Maximilian, Suleiman, Hani, Saunders, Brian T., Johnson, Michael W., Boehner, Alexander M. C., Viehmann, Susanne F., Theisen, Derek J., Kretzer, Nicole M., Briseno, Carlos G., Zaitsev, Konstantin, Ornatsky, Olga, Chang, Qing, Carrero, Javier A., Kopp, Jeffrey B., Artyomov, Maxim N., Kurts, Christian, Murphy, Kenneth M., Miner, Jeffrey H., Shaw, Andrey S., Brahler, Sebastian, Zinselmeyer, Bernd H., Raju, Saravanan, Nitschke, Maximilian, Suleiman, Hani, Saunders, Brian T., Johnson, Michael W., Boehner, Alexander M. C., Viehmann, Susanne F., Theisen, Derek J., Kretzer, Nicole M., Briseno, Carlos G., Zaitsev, Konstantin, Ornatsky, Olga, Chang, Qing, Carrero, Javier A., Kopp, Jeffrey B., Artyomov, Maxim N., Kurts, Christian, Murphy, Kenneth M., Miner, Jeffrey H., and Shaw, Andrey S.

Abstract

Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c(+) cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46(+) cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46(+) cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103(+) subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b(+) DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103(+) DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation.

Published
2018

28. Opposing Roles of Dendritic Cell Subsets in Experimental GN

Author

Brähler, Sebastian, primary, Zinselmeyer, Bernd H., additional, Raju, Saravanan, additional, Nitschke, Maximilian, additional, Suleiman, Hani, additional, Saunders, Brian T., additional, Johnson, Michael W., additional, Böhner, Alexander M.C., additional, Viehmann, Susanne F., additional, Theisen, Derek J., additional, Kretzer, Nicole M., additional, Briseño, Carlos G., additional, Zaitsev, Konstantin, additional, Ornatsky, Olga, additional, Chang, Qing, additional, Carrero, Javier A., additional, Kopp, Jeffrey B., additional, Artyomov, Maxim N., additional, Kurts, Christian, additional, Murphy, Kenneth M., additional, Miner, Jeffrey H., additional, and Shaw, Andrey S., additional

Published
2017
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30. Transcriptional Control of Dendritic Cell Development

Author

Murphy, Theresa L., primary, Grajales-Reyes, Gary E., additional, Wu, Xiaodi, additional, Tussiwand, Roxane, additional, Briseño, Carlos G., additional, Iwata, Arifumi, additional, Kretzer, Nicole M., additional, Durai, Vivek, additional, and Murphy, Kenneth M., additional

Published
2016
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33. Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+ conventional DC clonogenic progenitor

Author

Grajales-Reyes, Gary E, primary, Iwata, Arifumi, additional, Albring, Jörn, additional, Wu, Xiaodi, additional, Tussiwand, Roxane, additional, KC, Wumesh, additional, Kretzer, Nicole M, additional, Briseño, Carlos G, additional, Durai, Vivek, additional, Bagadia, Prachi, additional, Haldar, Malay, additional, Schönheit, Jörg, additional, Rosenbauer, Frank, additional, Murphy, Theresa L, additional, and Murphy, Kenneth M, additional

Published
2015
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34. MONDAY PUSHLIVE TEST L-Myc expression by dendritic cells is required for optimal T-cell priming

Author

KC, Wumesh, primary, Satpathy, Ansuman T., additional, Rapaport, Aaron S., additional, Briseño, Carlos G., additional, Wu, Xiaodi, additional, Albring, Jörn C., additional, Russler-Germain, Emilie V., additional, Kretzer, Nicole M., additional, Durai, Vivek, additional, Persaud, Stephen P., additional, Edelson, Brian T., additional, Loschko, Jakob, additional, Cella, Marina, additional, Allen, Paul M., additional, Nussenzweig, Michel C., additional, Colonna, Marco, additional, Sleckman, Barry P., additional, Murphy, Theresa L., additional, and Murphy, Kenneth M., additional

Published
2014
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35. Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate.

Author

Xiaodi Wu, Briseño, Carlos G., Grajales-Reyes, Gary E., Haldar, Malay, Arifumi Iwata, Kretzer, Nicole M., Wumesh K. C., Tussiwand, Roxane, Yujiro Higashi, Murphy, Theresa L., and Murphy, Kenneth M.

Subjects
ANTIGEN presenting cells, IMMUNOGLOBULIN producing cells, LYMPHOID tissue, PROTEINS, TRANSCRIPTION factors
Abstract

Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals. [ABSTRACT FROM AUTHOR]

Published
2016
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37. Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+ conventional DC clonogenic progenitor.

Author

Grajales-Reyes, Gary E, Iwata, Arifumi, Albring, Jörn, Wu, Xiaodi, Tussiwand, Roxane, KC, Wumesh, Kretzer, Nicole M, Briseño, Carlos G, Durai, Vivek, Bagadia, Prachi, Haldar, Malay, Schönheit, Jörg, Rosenbauer, Frank, Murphy, Theresa L, and Murphy, Kenneth M

Subjects
INTERFERON regulatory factors, CD8 antigen, DENDRITIC cells, TRANSCRIPTION factors, LABORATORY mice, CD4 antigen
Abstract

The transcription factors Batf3 and IRF8 are required for the development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions has remained unclear. Here we identified two progenitor cells positive for the transcription factor Zbtb46 that separately generated CD8α+ cDCs and CD4+ cDCs and arose directly from the common DC progenitor (CDP). Irf8 expression in CDPs required prior autoactivation of Irf8 that was dependent on the transcription factor PU.1. Specification of the clonogenic progenitor of CD8α+ cDCs (the pre-CD8 DC) required IRF8 but not Batf3. However, after specification of pre-CD8 DCs, autoactivation of Irf8 became Batf3 dependent at a CD8α+ cDC-specific enhancer with multiple transcription factor AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3−/− mice that were specified toward development into pre-CD8 DCs failed to complete their development into CD8α+ cDCs due to decay of Irf8 autoactivation and diverted to the CD4+ cDC lineage. [ABSTRACT FROM AUTHOR]

Published
2015
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38. The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain.

Author

Bowman-Kirigin JA, Desai R, Saunders BT, Wang AZ, Schaettler MO, Liu CJ, Livingstone AJ, Kobayashi DK, Durai V, Kretzer NM, Zipfel GJ, Leuthardt EC, Osbun JW, Chicoine MR, Kim AH, Murphy KM, Johanns TM, Zinselmeyer BH, and Dunn GP

Subjects
Animals, Mice, CD8-Positive T-Lymphocytes, Antigens, Neoplasm, Brain, Dendritic Cells, Neoplasms
Abstract

The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to the choroid plexus and dura. Thus, whether the cDC1 play a function in presenting antigen derived from parenchymal sources in the tumor setting remains unknown. Using preclinical glioblastoma (GBM) models and cDC1-deficient mice, we explored the presently unknown role of cDC1 in CNS antitumor immunity. We determined that, in addition to infiltrating the brain tumor parenchyma itself, cDC1 prime neoantigen-specific CD8+ T cells against brain tumors and mediate checkpoint blockade-induced survival benefit. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1 equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same APC subsets, we identified a tumor-specific fluorescent metabolite of 5-aminolevulinic acid, which fluorescently labeled tumor cells during fluorescence-guided GBM resection. Together, these data elucidate the specialized behavior of cDC1 and suggest that cDC1 play a significant role in CNS antitumor immunity., (©2022 American Association for Cancer Research.)

Published
2023
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39. Opposing Roles of Dendritic Cell Subsets in Experimental GN.

Author

Brähler S, Zinselmeyer BH, Raju S, Nitschke M, Suleiman H, Saunders BT, Johnson MW, Böhner AMC, Viehmann SF, Theisen DJ, Kretzer NM, Briseño CG, Zaitsev K, Ornatsky O, Chang Q, Carrero JA, Kopp JB, Artyomov MN, Kurts C, Murphy KM, Miner JH, and Shaw AS

Subjects
Animals, Antigens, CD metabolism, Basic-Leucine Zipper Transcription Factors genetics, CD11 Antigens genetics, CD11b Antigen genetics, Cell Movement, Chemokine CXCL2 genetics, Dendritic Cells metabolism, Dendritic Cells pathology, Gene Expression, Genes, Reporter, Green Fluorescent Proteins metabolism, Integrin alpha Chains metabolism, Macrophages, Male, Mice, Mice, Knockout, Neutrophils pathology, Neutrophils physiology, Repressor Proteins genetics, Sequence Analysis, RNA, Sorting Nexins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transcriptome, Dendritic Cells physiology, Glomerulonephritis immunology, Glomerulonephritis pathology
Abstract

Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46 -GFP and Snx22 -GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c + cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46 -GFP or Snx22 -GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46 + cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46 + cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103 + subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b + DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103 + DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation., (Copyright © 2018 by the American Society of Nephrology.)

Published
2018
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