| 61. |
- Lucas, Beth, et al.
(författare)
-
CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice
- 2015
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 45:2, s. 574-583
-
Tidskriftsartikel (refereegranskat)abstract
- Thymus colonisation and thymocyte positioning are regulated by interactions between CCR7 and CCR9, and their respective ligands, CCL19/CCL21 and CCL25. The ligands of CCR7 and CCR9 also interact with the atypical receptor CCRL1 (also known as ACKR4), which is expressed in the thymus and has recently been reported to play an important role in normal alpha beta T-cell development. Here, we show that CCRL1 is expressed within the thymic cortex, predominantly by MHC-II(low)CD40(-) cortical thymic epithelial cells and at the subcapsular zone by a population of podoplanin(+) thymic epithelial cells in mice. Interestingly, CCRL1 is also expressed by stromal cells which surround the pericytes of vessels at the corticomedullary junction, the site for progenitor cell entry and mature thymocyte egress from the thymus. We show that CCRL1 suppresses thymocyte progenitor entry into the thymus, however, the thymus size and cellularity are the same in adult WT and CCRL1(-/-) mice. Moreover, CCRL1(-/-) mice have no major perturbations in T-cell populations at different stages of thymic differentiation and development, and have a similar rate of thymocyte migration into the blood. Collectively, our findings argue against a major role for CCRL1 in normal thymus development and function.
|
|
| 62. |
- Lukin, Kara, et al.
(författare)
-
A dose-dependent role for EBF1 in repressing non-B-cell-specific genes
- 2011
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 41:6, s. 1787-1793
-
Tidskriftsartikel (refereegranskat)abstract
- In the absence of early B-cell factor 1 (EBF1), B-cell development is arrested at an uncommitted progenitor stage that exhibits increased lineage potentials. Previously, we investigated the roles of EBF1 and its DNA-binding partner Runx1 by evaluating B lymphopoiesis in single (EBF1(het) and Runx1(het)) and compound haploinsufficent (Ebf1(+/-) Runx1(+/-), ERhet) mice. Here, we demonstrate that decreased Ebf1 gene dosage results in the inappropriate expression of NK-cell lineage-specific genes in B-cell progenitors. Moreover, prolonged expression of Ly6a/Sca-1 suggested the maintenance of a relatively undifferentiated phenotype. These effects were exacerbated by reduced expression of Runx1 and occurred despite expression of Pax5. Repression of inappropriately expressed genes was restored in most pre-B and all immature B cells of ERhet mice. Enforced EBF1 expression repressed promiscuous transcription in pro-B cells of ERhet mice and in Ebf1(-/-) Pax5(-/-) fetal liver cells. Together, our studies suggest that normal levels of EBF1 are critical for maintaining B-cell identity by directing repression of non-B-cell-specific genes.
|
|
| 63. |
|
|
| 64. |
- Manivel, Vivek Anand, 1988-, et al.
(författare)
-
Granulocyte-augmented chemokine production induced by type II collagen containing immune complexes is mediated via TLR4 in rheumatoid arthritis patients
- 2016
-
Ingår i: European Journal of Immunology. - : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 46:12, s. 2822-2834
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) patients with early elevations of antibodies against collagen type II (CII) have a distinct acute onset phenotype, associated with cytokine induction by surface-bound anti-CII-containing immune complexes (ICs) and high C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Polymorphonuclear granulocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) are abundant in the vicinity of CII in RA joints, and both PMN and PBMC reactivity against anti-CII IC individually relate to early joint destruction and early elevation of CRP and ESR in RA. We searched for CII-dependent mechanisms that might attract PMNs and PBMCs to RA joints. Human PBMCs and PMNs were stimulated with anti-CII ICs and control ICs, either individually or in cocultures. Cocultured PMNs and PBMCs stimulated with anti-CII ICs synergistically augmented production of the chemokines CXCL8, RANTES and MCP-1, whereas downregulation was seen with control IC. This upregulation was unique to chemokines, as TNF-α, IL-1β, and GM-CSF were downregulated in anti-CII IC-stimulated cocultures. The coculture-associated chemokine upregulation depended on endogenous TLR4 ligand(s) and functionally active PMN enzymes, and was partially mediated by GM-CSF. As anti-CII levels peak around the time of RA diagnosis, this mechanism can attract inflammatory cells to joints in early RA and intensify the anti-CII-associated acute onset RA phenotype.
|
|
| 65. |
- Marks, Ellen, 1982, et al.
(författare)
-
CD4(+) T-cell immunity in the female genital tract is critically dependent on local mucosal immunization.
- 2011
-
Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 41:9, s. 2642-53
-
Tidskriftsartikel (refereegranskat)abstract
- Immunizations via the i.n. and intravaginal (ivag) routes effectively generate strong genital tract antibody-mediated immunity. To what extent the same is true for T-cell responses is incompletely known. Therefore, we set out to investigate optimal conditions for stimulation of genital tract CD4(+) T-cell responses, using adoptive transfer of mouse DO11.10 TCR transgenic T cells specific for OVA and OVA conjugated to cholera toxin (CT) as an immunogen. We observed that progesterone was required for a T-cell response following ivag immunization, whereas estradiol prevented a response. Although i.n. immunization stimulated OVA-specific CD4(+) T-cell responses in the draining LNs, it was substantially less effective compared to ivag. More importantly, an ivag booster immunization was absolutely required to attract T cells to the genital tract mucosa itself. While clinical use of CT is precluded because of its toxicity, we developed a combined adjuvant vector based on a non-toxic derivative of CT and immune-stimulating complexes. The CTA1-DD/immune-stimulating complexes (ISCOMs) adjuvant together with major outer membrane protein was effective at stimulating genital tract CD4(+) T-cell immunity and protection against a live chlamydial infection, which holds promise for the development of mucosal vaccines against sexually transmitted infections.
|
|
| 66. |
- Mazurek, Jolanta, et al.
(författare)
-
Mycobacteria-infected bystander macrophages trigger maturation of dendritic cells and enhance their ability to mediate HIV transinfection
- 2012
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 42:5, s. 1192-1202
-
Tidskriftsartikel (refereegranskat)abstract
- Synergistic interplay between Mycobacterium tuberculosis (Mtb) and HIV in coinfected ind-ividuals leads to the acceleration of both tuberculosis and HIVdisease. Mtb, as well as HIV, may modulate the function of many immune cells, including DCs. To dissect the bystander impact of Mfs infected with Mtb on DC functionality, we here investigated changes in DC phenotype, cytokine profiles, and HIV-1 transinfecting ability. An in vitro system was used in which human monocyte-derived DCs were exposed to soluble factors released by Mfs infected with mycobacteria, including virulent clinical Mtb isolates and nonvirulent BCG. Soluble factors secreted from Mtb-infected Mfs, and to a lesser extent BCG-infected Mfs, resulted in the production of proinflammatory cytokines and partial upregulation of DC maturation markers. Interestingly, the HIV-1 transinfecting ability of DCs was enhanced upon exposure to soluble factors released by Mtb-infected Mfs. In summary, our study shows that DCs exposed to soluble factors released by mycobacteria-infected Mfs undergo maturation and display an augmented ability to transmit HIV-1 in trans. These findings highlight the important role of bystander effects during the course of MtbHIV coinfection and suggest that Mtb-infected Mfs may contribute to an environment that supports DC-mediated spread and amplification of HIV in coinfected individuals.
|
|
| 67. |
- Mazzurana, Luca, et al.
(författare)
-
Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3−ILC1/NK cell transdifferentiation
- 2019
-
Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 202:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Ikaros family of transcription factors (TFs) are important regulators of lymphocyte function. However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (IKZF1) is expressed by all ILC subsets, including NK cells, in blood, tonsil, and gut, while Helios (IKZF2) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (IKZF3) followed the expression pattern of T-bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN-γ-producing ILC1 and NK cells from ILC3 by IL-1β plus IL-12-stimulation was associated with upregulation of T-bet and Aiolos. Selective degradation of Aiolos and Ikaros by lenalidomide suppressed ILC1 and NK cell differentiation and expression of ILC1 and NK cell-related transcripts (LEF1, PRF1, GRZB, CD244, NCR3, and IRF8). In line with reduced ILC1/NK cell differentiation, we observed an increase in the expression of the ILC3-related TF Helios, as well as ILC3 transcripts (TNFSF13B, IL22, NRP1, and RORC) and in the frequency of IL-22 producing ILC3 in cultures with IL-1β and IL-23. These data suggest that suppression of Aiolos and Ikaros expression inhibits ILC1 and NK cell differentiation while ILC3 function is maintained. Hence, our results open up for new possibilities in targeting Ikaros family TFs for modulation of type 1/3 immunity in inflammation and cancer.
|
|
| 68. |
|
|
| 69. |
|
|
| 70. |
- Mohlin, Frida, et al.
(författare)
-
Analysis of genes coding for CD46, CD55 and C4b-binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss.
- 2013
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 43:6, s. 1617-1629
-
Tidskriftsartikel (refereegranskat)abstract
- Since a tightly regulated complement system is needed for a successful pregnancy, we hypothesized that alterations in complement inhibitors may be associated with idiopathic, recurrent miscarriage. We sequenced all exons coding for three complement inhibitors: C4b-binding protein (C4BP), CD46 and CD55 in 384 childless women with at least two miscarriages that could not be explained by known risk factors. Several alterations were found in C4BPA, of which the R120H, I126T, and the G423T mutations affected the expression level and/or the ability of recombinant C4BP to serve as cofactor for factor I. The only variant in C4BPB was located in the C-terminal part, and did not impair the polymerization of the molecule. Our results identify for the first time alterations in C4BP in women experiencing recurrent miscarriages. We also found four CD46 alterations in individual patients that were not found in healthy controls. One of the rare variants, P324L, showed decreased expression, whereas N213I resulted in deficient protein processing as well as an impaired cofactor activity in the degradation of both C4b and C3b. The identified alterations may result in in vivo consequences and contribute to the disorder but the degree of association must be evaluated in larger cohorts.
|
|
