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CD103+ dendritic cell

Anne Dommaschk, Lara F Lang, Regina Maus, Jennifer Stolper, Tobias Welte, Ulrich A Maus
Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice...
March 15, 2018: European Journal of Immunology
Rachel Mak'Anyengo, Peter Duewell, Cornelia Reichl, Christine Hörth, Hans-Anton Lehr, Sandra Fischer, Thomas Clavel, Gerald Denk, Simon Hohenester, Sebastian Kobold, Stefan Endres, Max Schnurr, Christian Bauer
Inflammatory bowel disease (IBD) is associated with enhanced levels of the IL-1 family cytokines IL-1β and IL-18, which are activated by the Nlrp3 inflammasome. Here, we investigated the role of inflammasome-driven cytokine release on T cell polarization and DC differentiation in steady state and T cell transfer colitis. In vitro and in vivo data showed that IL-1β induces Th17 polarization and increases GM‑CSF production by T cells. Reduced IL-1β levels in Nlrp3-/- mice correlated with enhanced FLT3L levels and increased frequency of tolerogenic CD103+ DC...
March 8, 2018: JCI Insight
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Ivo S Hansen, Lisette Krabbendam, Jochem H Bernink, Fabricio Loayza-Puch, Willianne Hoepel, Johan A van Burgsteden, Elsa C Kuijper, Christianne J Buskens, Willem A Bemelman, Sebastiaan A J Zaat, Reuven Agami, Gestur Vidarsson, Gijs R van den Brink, Esther C de Jong, Manon E Wildenberg, Dominique L P Baeten, Bart Everts, Jeroen den Dunnen
CD103+ dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103+ SIRPα+ DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103+ DCs...
February 28, 2018: Nature Communications
Leticia Tordesillas, M Cecilia Berin
Oral tolerance is a state of systemic unresponsiveness that is the default response to food antigens in the gastrointestinal tract, although immune tolerance can also be induced by other routes, such as the skin or inhalation. Antigen can be acquired directly by intestinal phagocytes, or pass through enterocytes or goblet cell-associated passages prior to capture by dendritic cells (DCs) in the lamina propria. Mucin from goblet cells acts on DCs to render them more tolerogenic. A subset of regulatory DCs expressing CD103 is responsible for delivery of antigen to the draining lymph node and induction of Tregs...
February 27, 2018: Clinical Reviews in Allergy & Immunology
Yeon Duk Woo, Jaemoon Koh, Hye-Ryun Kang, Hye Young Kim, Doo Hyun Chung
BACKGROUND: The XCL1-XCR1 axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in allergic asthma. OBJECTIVE: In the present study, we explored that the iNKT cell-mediated XCL1-XCR1 axis regulated the allergic asthma. METHODS: Ovalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice. RESULTS: XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103+ dendritic cells (DCs), and Th2 responses in the lungs compared with wild-type (WT) mice during OVA or HDM-induced asthma...
February 20, 2018: Journal of Allergy and Clinical Immunology
Marta Rodriguez-Garcia, Jared M Fortier, Fiona D Barr, Charles R Wira
As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103+ CD8+ long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+ CD8+ T cells were increased in postmenopausal compared to premenopausal women...
February 18, 2018: Aging Cell
Irene Soleto, Uwe Fischer, Carolina Tafalla, Aitor G Granja
Dendritic cells (DCs) are highly specialized antigen-presenting cells that bridge innate and adaptive immune responses in vertebrates, being key modulators in the initiation of specific responses. Although teleost fish present the main elements of a fully developed adaptive immune system, not many studies have focused on identifying specific DC subsets in teleost species. Previous work from our group identified in rainbow trout (Oncorhynchus mykiss) skin a DC subpopulation co-expressing CD8α and major histocompatibility complex II β on the cell surface...
2018: Frontiers in Immunology
Susan van Aalst, Manon A A Jansen, Irene S Ludwig, Ruurd van der Zee, Willem van Eden, Femke Broere
Most traditional vaccines are administered via the intramuscular route. Other routes of administration however, can induce equal or improved protective memory responses and might provide practical advantages such as needle-free immunization, dose sparing and induction of tissue-specific (mucosal) immunity. Here we explored the differences in immunological outcome after immunization with model antigens via two promising immunization routes (intradermal and intranasal) with or without the experimental adjuvant and TLR7/8-agonist R848...
February 3, 2018: Vaccine
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
Frederick Allen, Iuliana D Bobanga, Peter Rauhe, Deborah Barkauskas, Nathan Teich, Caryn Tong, Jay Myers, Alex Y Huang
Inflammatory chemokines are critical contributors in attracting relevant immune cells to the tumor microenvironment and driving cellular interactions and molecular signaling cascades that dictate the ultimate outcome of host anti-tumor immune response. Therefore, rational application of chemokines in a spatial-temporal dependent manner may constitute an attractive adjuvant in immunotherapeutic approaches against cancer. Existing data suggest that the macrophage inflammatory protein (MIP)-1 family and related proteins, consisting of CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES), can be major determinant of immune cellular infiltration in certain tumors through their direct recruitment of antigen presenting cells, including dendritic cells (DCs) to the tumor site...
2018: Oncoimmunology
Rocky Lai, Mangalakumari Jeyanathan, Sam Afkhami, Anna Zganiacz, Joanne A Hammill, Yushi Yao, Charu Kaushic, Zhou Xing
Mycobacterium tuberculosis, the pathogen causing pulmonary tuberculosis (TB) in humans, has evolved to delay Th1 immunity in the lung. Although conventional dendritic cells (cDCs) are known to be critical to the initiation of T cell immunity, the differential roles and molecular mechanisms of migratory CD11b+ and CD103+ cDC subsets in anti-M. tuberculosis Th1 activation remain unclear. Using a murine model of pulmonary M. tuberculosis infection, we found that slow arrival of M. tuberculosis-bearing migratory CD11b+ and CD103+ cDCs at the draining lymph nodes preceded the much-delayed Th1 immunity and protection in the lung...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Hisashi Ueta, Yusuke Kitazawa, Yasushi Sawanobori, Takamasa Ueno, Satoshi Ueha, Kouji Matsushima, Kenjiro Matsuno
Donor-specific blood transfusion is known to induce alloresponses and lead to immunosuppression. We examined their underlying mechanisms by employing fully allogeneic rat combinations. Transfused recipients efficiently produced alloantibodies of the IgM and IgG subclasses directed against donor class I MHC. The recipients exhibited active expansion of CD4+ T-cells and CD4+FOXP3+ Treg cells, followed by CD45R+ B-cells and IgM+ or IgG subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the resident MHCII+CD103+ dendritic cells in the splenic T-cell area, periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl-2'-deoxyuridine+ cells, from which the proliferative response of CD4+ T-cells originated peaking at 3-4 days...
January 18, 2018: International Immunology
Nobuo Fuke, Tomohisa Takagi, Yasuki Higashimura, Toshifumi Tsuji, Ryohei Umeda, Katsura Mizushima, Makoto Tanaka, Hiroyuki Suganuma, Koichi Aizawa, Nobuhiro Yajima, Yuji Naito
Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal inflammation. Little is known about how the ratio is regulated by lactic acid bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of LAB/Bif to this ratio. Methods: We established an in vitro experimental system using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective LAB/Bif strains...
January 18, 2018: Inflammatory Bowel Diseases
Sonia Rehal, Matthew Stephens, Simon Roizes, Shan Liao, Pierre-Yves von der Weid
Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS)...
December 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
A Flores-Langarica, K Müller Luda, E K Persson, C N Cook, S Bobat, J L Marshall, M W Dahlgren, K Hägerbrand, K M Toellner, M D Goodall, D R Withers, I R Henderson, B Johansson Lindbom, A F Cunningham, W W Agace
Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses...
December 20, 2017: Mucosal Immunology
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
Madhav D Sharma, Paulo C Rodriguez, Brent H Koehn, Babak Baban, Yan Cui, Gang Guo, Michiko Shimoda, Rafal Pacholczyk, Huidong Shi, Eun-Joon Lee, Hongyan Xu, Theodore S Johnson, Yukai He, Taha Mergoub, Christopher Venable, Vincenzo Bronte, Jedd D Wolchok, Bruce R Blazar, David H Munn
CD103+ dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic precursors. These Ly6c+ CD103+ cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c+ CD103+ phenotype...
January 16, 2018: Immunity
Jun Kuwabara, Akihiro Umakoshi, Naoki Abe, Yutaro Sumida, Shota Ohsumi, Eika Usa, Kana Taguchi, Mohammed E Choudhury, Hajime Yano, Shirabe Matsumoto, Takeharu Kunieda, Hisaaki Takahashi, Toshihiro Yorozuya, Yuji Watanabe, Junya Tanaka
CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted...
January 12, 2018: Biochemical and Biophysical Research Communications
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
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