| 1. |
- Bain, C. C., et al.
(författare)
-
Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors
- 2013
-
Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 6:3, s. 498-510
-
Tidskriftsartikel (refereegranskat)abstract
- Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.
|
|
| 2. |
- Holmkvist, Petra, et al.
(författare)
-
A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
- 2015
-
Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:3, s. 545-558
-
Tidskriftsartikel (refereegranskat)abstract
- Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.
|
|
| 3. |
- Jaensson Gyllenbäck, Elin, et al.
(författare)
-
Small intestinal CD103(+) dendritic cells display unique functional properties that are conserved between mice and humans
- 2008
-
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:9, s. 2139-2149
-
Tidskriftsartikel (refereegranskat)abstract
- A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and alpha 4 beta 7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI- LP. BrdU pulse-chase experiments suggested that most CD103(+) DCs do not derive from a CD103(-) SI- LP DC intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue- derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(+) MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs isolated from SB Crohn ' s patients. Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal infl ammatory responses.
|
|
| 4. |
- Jones, Hannah E., et al.
(författare)
-
The differential response of human dendritic cells to live and killed Neisseria meningitidis
- 2007
-
Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814. ; 9:12, s. 2856-2869
-
Tidskriftsartikel (refereegranskat)abstract
- There is currently no effective vaccine for Neisseria meningitidis (Nm) serogroup B. Generation of optimal immune responses to meningococci could be achieved by targeting meningococcal antigens to human dendritic cells (DCs). Recent studies have shown that diverse DC responses and subsequent generation of protective immunity can be observed if the microbes are viable or killed. This is important because the host is likely to be exposed to both live and killed bacteria during natural infection. There are currently few data on comparative DC responses to live and killed meningococci. We show here that exposure of human DC to live meningococci does not result in a typical maturation response, as determined by the failure to upregulate CD40, CD86, HLA-DR and HLA-Class I. Despite this, live meningococci were potent inducers of IL-12 and IL-10, although the ratios of these cytokines differed from those to killed organisms. Our data also suggest that enhanced phagocytosis of killed organisms compared with live may be responsible for the differential cytokine responses, involving an autocrine IL-10-dependent mechanism. The consequences of these findings upon the effectiveness of antigen presentation and T-cell responses are currently under investigation.
|
|
| 5. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
Macrophage and dendritic cell subsets in IBD: ALDH cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation
- 2016
-
Ingår i: Mucosal Immunology. - : Elsevier BV. - 1935-3456 .- 1935-3456 .- 1933-0219. ; 9:1, s. 171-182
-
Tidskriftsartikel (refereegranskat)abstract
- Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14- DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.
|
|
| 6. |
- Persson, Emma, et al.
(författare)
-
IRF4 Transcription-Factor-Dependent CD103(+)CD11b(+) Dendritic Cells Drive Mucosal T Helper 17 Cell Differentiation.
- 2013
-
Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 38:5, s. 958-969
-
Tidskriftsartikel (refereegranskat)abstract
- CD103(+)CD11b(+) dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103(+)CD11b(+) DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes (MLN) following immunization. The latter was associated with a selective reduction in CD103(+)CD11b(+) MLN DCs and DC derived IL-6. Immunized Il6(-/-) mice failed to support Th17 cell differentiation in MLN in vivo and CD103(+)CD11b(+) MLN DCs supported IL-6-dependent Th17 cell differentiation in vitro. Together, our results suggest a central role for IRF4-dependent, IL-6 producing CD103(+)CD11b(+) DCs in intestinal Th17 cell differentiation.
|
|
| 7. |
- Poulin, Lionel F., et al.
(författare)
-
DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues
- 2012
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 119:25, s. 6052-6062
-
Tidskriftsartikel (refereegranskat)abstract
- Mouse CD8 alpha(+) dendritic cells (DCs) in lymphoid organs and CD103(+) CD11b(-) DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8 alpha(+) DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8 alpha(+) DC has recently b een questioned. Furthermore, the identification of "CD8 alpha(+) DC-like" cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage members. Here we show that mouse CD8 alpha(+) DCs and CD103(+) CD11b(-) DCs can be defined by shared high expression of DNGR-1 (CLEC9A). We further show that DNGR-1 uniquely marks a CD11b(-) human DC population present in both lymphoid and nonlymphoid tissues of humans and humanized mice. Finally, we demonstrate that knockdown of Batf3 selectively prevents the development of DNGR-1(+) human DCs in vitro. Thus, high expression of DNGR-1 specifically and universally identifies a unique DC subset in mouse and humans. Evolutionarily conserved Batf3 dependence justifies classification of DNGR-1(hi) DCs as a distinct DC lineage. (Blood. 2012; 119(25): 6052-6062)
|
|
| 8. |
- Samuelsson, Malin, et al.
(författare)
-
RhoB controls the Rab11-mediated recycling and surface reappearance of LFA-1 in migrating T lymphocytes
- 2017
-
Ingår i: Science Signaling. - Washington, DC, USA : American Association for the Advancement of Science (A A A S). - 1945-0877 .- 1937-9145. ; 10:509
-
Tidskriftsartikel (refereegranskat)abstract
- The regulation of cell adhesion and motility is complex and requires the intracellular trafficking of integrins to and from sites of cell adhesion, especially in fast-moving cells such as leukocytes. The Rab family of guanosine triphosphatases (GTPases) is essential for vesicle transport, and vesicles mediate intracellular integrin trafficking. We showed that RhoB regulates the vesicular transport of the integrin LFA-1 along the microtubule network in migrating T lymphocytes. Impairment in RhoB function resulted in the accumulation of both LFA-1 and the recycling endosomal marker Rab11 at the rear of migrating T lymphocytes and decreased the association between these molecules. T lymphocytes lacking functional RhoB exhibited impaired recycling and subsequently decreased surface amounts of LFA-1, leading to reduced T cell adhesion and migration mediated by the cell adhesion molecule ICAM-1 (intercellular adhesion molecule-1). We propose that vesicle-associated RhoB is a regulator of the Rab11-mediated recycling of LFA-1 to the cell surface, an event that is necessary for T lymphocyte motility.
|
|
| 9. |
- Semmrich, Monika, et al.
(författare)
-
Directed antigen targeting in vivo identifies a role for CD103(+) dendritic cells in both tolerogenic and immunogenic T-cell responses.
- 2012
-
Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 5:2, s. 150-60
-
Tidskriftsartikel (refereegranskat)abstract
- The αE integrin chain CD103 identifies a subset of migratory dendritic cells (DCs) in the gut, lung, and skin. To gain further understanding of the function of CD103(+) DCs in regulating adaptive immunity in vivo, we coupled ovalbumin (OVA) to the CD103 antibody M290 (M290.OVA). Intraperitoneal injection of M290.OVA induced OVA-specific CD8(+) and CD4(+) T-cell proliferation in lymph nodes (LNs) of wild-type but not CD103(-/-) mice, or in mice depleted of CD11c(+) cells. In the absence of maturation stimuli, systemic antigen targeting to CD103(+) DCs led to tolerance of CD8(+) T cells, whereas coadministration of adjuvant induced cytotoxic T-lymphocyte (CTL) immunity and antibody production. Mucosal intratracheal application of M290.OVA also induced T-cell proliferation in mediastinal LNs, yet the functional outcome was tolerance that inhibited subsequent development of allergic airway inflammation and immunoglobulin E (IgE) responses to inhaled OVA. These findings identify antigen targeting to CD103(+) DCs as a potential strategy to regulate immune responses in nonlymphoid mucosal tissues.
|
|
| 10. |
- Sitnik, Katarzyna M, et al.
(författare)
-
Context-Dependent Development of Lymphoid Stroma from Adult CD34(+) Adventitial Progenitors.
- 2016
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 14:10, s. 2375-2388
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3(-)PDPN(+)PDGFRβ(+)/α(+)CD34(+) stromal adventitial cells in both lymph nodes (LNs) and thymus that is located within the vascular niche surrounding PDPN(-)PDGFRβ(+)/α(-)Esam-1(+)ITGA7(+) pericytes. CD34(+) adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34(+) adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDC-like cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34(+) adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.
|
|
