Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Monocytes/macrophages (MΦ), considered as plastic cells, can differentiate into either a pro-inflammatory (M1) subtype, also known as a classically activated subtype, or an anti-inflammatory alternatively activated subtype (M2) according to their microenvironment. Phenotypic markers of mouse polarized MΦ have been extensively studied, whereas their human counterparts remain less characterized. The main goal of this study was therefore to carefully characterize phenotypic and genomic markers of primary human MΦ generated from M-CSF-treated blood monocytes and polarized towards M1 or M2 subtype upon the action of lipopolysaccharide and interferon-γ (for M1) or interleukin (IL)-4 (for M2). Membrane expression of the markers CD80 and CD200R was found to be specific of human M1 and M2 polarized MΦ, respectively, whereas, by contrast, mannose receptor (CD206) expression did not discriminate between M1 and M2. mRNA expression analysis further identified six markers of M1 polarization (IL-12p35, CXCL10, CXCL11, CCL5, CCR7 and IDO1), five markers of M2 polarization (TGF-β, CCL14, CCL22, SR-B1 and PPARγ) and transcription factors involved in MΦ polarization. Ability of human M-CSF-generated MΦ to polarize toward M1 or M2 subtype was also associated with enhanced secretion of TNFα, IL-1β, IL-12p40, CXCL10 and IL-10 (for M1) or CCL22 (for M2). Moreover, the comparison of the expression of M1 markers in M-CSF- and GM-CSF-MΦ polarized towards M1 subtype has revealed similarities. In conclusion, we demonstrated that human M-CSF MΦ can polarize toward a M1 type after IFNγ/LPS stimulation. Moreover, the M1 and M2 markers of human polarized MΦ identified in the present study may be useful to better identify human MΦ subtypes, particularly at the tissue level, in order to better understand their respective roles in the development of pathologies.
ISSN: 0008-8749

inserm-00823273
http://www.hal.inserm.fr/inserm-00823273
DOI : 10.1016/j.cellimm.2013.01.010
PUBMED : 23454681

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Dengue fever is the most important arboviral infection that affects humans, particularly in tropical and subtropical regions. Here, we provide the first comprehensive overview of the severity of dengue epidemics in French Guiana. METHODOLOGY/PRINCIPAL FINDINGS: We monitored hospitalized cases between 2008 and 2013. Detailed clinical features and biological parameters were collected on a daily basis from all cases. Among the 1,356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. The severity rates were similar between the three major epidemics that occurred during the study period, whereas the hospitalization rate was highest in 2013. Fluid accumulation, aspartate aminotransferase (ASAT) counts>193 IU/L and platelet counts<75,000 cells/mm3 were associated with dengue severity. CONCLUSIONS/SIGNIFICANCE: Our findings provide a recent epidemiological description of the severity of dengue epidemics in French Guiana. These results highlight the potential impacts and consequences of implementing the WHO 2009 classification on hospital activity. Future studies should include virological and immunological investigations of well-documented serum samples.
ISSN: 1932-6203

hal-01477201
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477201
DOI : 10.1371/journal.pone.0172267
PUBMED : 28196111

Éditeur(s) : HAL CCSD Springer Verlag (Germany)
Résumé : International audience
Tight control of basal cytosolic Ca(2+) concentration is essential for cell survival and to fine-tune Ca(2+)-dependent cell functions. A way to control this basal cytosolic Ca(2+) concentration is to regulate membrane Ca(2+) channels including store-operated Ca(2+) channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca(2+) channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca(2+) channels contributes to Ca(2+) entry and the transient increase in cytosolic Ca(2+) concentration involved in intracellular signaling. However, in various experimental conditions, Ca(2+) entry and/or Ca(2+) currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca(2+) channels are already open/activated in basal condition, contributing therefore to constitutive Ca(2+) entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.
ISSN: 0175-7571

hal-01528591
https://hal.archives-ouvertes.fr/hal-01528591
DOI : 10.1007/s00249-017-1216-8
PUBMED : 28516266

Éditeur(s) : HAL CCSD Elsevier
Résumé : The Duffy antigen/receptor for chemokine (DARC) is an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi) and for chemokines. In contrast to other chemokine receptors, DARC is a promiscuous receptor that binds chemokines of both CC and CXC classes. The four extracellular domains (ECDs) of DARC are essential for its interaction with chemokines, whilst the first (ECD1) is sufficient for the interaction with malaria erythrocyte-binding protein. In this study, we elaborate and analyze structural models of the DARC. The construction of the 3D models is based on a comparative modeling process and on the use of many procedures to predict transmembrane segments and to detect far homologous proteins with known structures. Threading, ab initio, secondary structure and Protein Blocks approaches are used to build a very large number of models. The conformational exploration of the ECDs is performed with simulated annealing. The second and fourth ECDs are strongly constrained. On the contrary, the ECD1 is highly flexible, but seems composed of three consecutive regions: a small beta-sheet, a linker region and a structured loop. The chosen structural models encompass most of the biochemical features and reflect the known experimental data. They may be used to analyze functional interaction properties.
ISSN: 0006-3002

inserm-00143373
http://www.hal.inserm.fr/inserm-00143373
http://www.hal.inserm.fr/inserm-00143373/document
http://www.hal.inserm.fr/inserm-00143373/file/de_Brevern_BBA_2005.pdf
DOI : 10.1016/j.bbagen.2005.05.016

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. DESIGN AND METHODS: In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. RESULTS: In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). CONCLUSION: In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination.
ISSN: 0269-9370

hal-00875148
https://hal.archives-ouvertes.fr/hal-00875148
DOI : 10.1097/QAD.0b013e328359f27a
PUBMED : 23018437

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Homing of CD8+ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGF-β is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8+ T lymphocytes. However, the interplay between TGF-β and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGF-β enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGF-β bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGF-β in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer
ISSN: 0008-5472

Droits : info:eu-repo/semantics/OpenAccess
hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/file/TGF%CE%B2%20Signaling%20Intersects%20with%20CD103-boutet2016-final.pdf
DOI : 10.1158/0008-5472.CAN-15-1545

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-κB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.
ISSN: 0892-6638

hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/file/Soluble%20CD14%20acts%20as%20a%20DAMP%20in%20human-accepted.pdf
PUBMED : 28122919

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND:Dengue fever is the most important arboviral infection that affects humans, particularly in tropical and subtropical regions. Here, we provide the first comprehensive overview of the severity of dengue epidemics in French Guiana.METHODOLOGY/PRINCIPAL FINDINGS:We monitored hospitalized cases between 2008 and 2013. Detailed clinical features and biological parameters were collected on a daily basis from all cases. Among the 1,356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. The severity rates were similar between the three major epidemics that occurred during the study period, whereas the hospitalization rate was highest in 2013. Fluid accumulation, aspartate aminotransferase (ASAT) counts>193 IU/L and platelet counts<75,000 cells/mm3 were associated with dengue severity.CONCLUSIONS/SIGNIFICANCE:Our findings provide a recent epidemiological description of the severity of dengue epidemics in French Guiana. These results highlight the potential impacts and consequences of implementing the WHO 2009 classification on hospital activity. Future studies should include virological and immunological investigations of well-documented serum samples
ISSN: 1932-6203

inserm-01481447
http://www.hal.inserm.fr/inserm-01481447
http://www.hal.inserm.fr/inserm-01481447/document
http://www.hal.inserm.fr/inserm-01481447/file/2017%2C%20Flamand%20-%20Epidemiological%20assessment%20of%20the%20severity%20of%20dengue%20epidemics%20in%20French%20Guiana.pdf
DOI : 10.1371/journal.pone.0172267.t003

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVES: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). DESIGN AND METHODS: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. RESULTS: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. CONCLUSION: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.
ISSN: 0269-9370

hal-00875175
https://hal.archives-ouvertes.fr/hal-00875175
DOI : 10.1097/QAD.0b013e32835844d9
PUBMED : 22842994

Éditeur(s) : HAL CCSD
Résumé : International audience
Human polycystic echinococcosis is a parasitic infection caused by the larval stage of Echinococcus vogeli which occurs in rural areas of Central and South America. Abdominal echinococcosis caused by E. vogeli is reported for the first time in a child, a 6-year-old boy in French Guiana. The diagnosis was made by histological and molecular techniques. In tropical regions, this neglected disease must be considered even in children.
ISSN: 2046-9047

hal-01484299
https://hal.univ-lorraine.fr/hal-01484299
DOI : 10.1179/2046905515Y.0000000054

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The underlying cause of morbidity in cystic fibrosis (CF) is the decline in lung function, which results in part from chronic inflammation. Inflammation and infection occur early in infancy in CF and the role of innate immune defense in CF has been highlighted in the last years. Once thought simply to be consumers of bacteria, macrophages have emerged as highly sensitive immune cells that are located at the balance point between inflammation and resolution of this inflammation in CF pathophysiology. In order to assess the potential role of macrophage in CF, we review the evidence that: (1) CF macrophage has a dysregulated inflammatory phenotype; (2) CF macrophage presents altered phagocytosis capacity and bacterial killing; and (3) lipid disorders in CF macrophage affect its function. These alterations of macrophage weaken innate defense of CF patients and may be involved in CF disease progression and lung damage.
ISSN: 1569-1993

hal-01560280
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560280
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560280/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560280/file/Chouly-The%20impact%20of%20impaired%20macrophage%20functions.pdf
DOI : 10.1016/j.jcf.2016.10.011

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. Several mechanisms are supposed to contribute to this susceptibility. The exact reasons of the propensity of sickle cell patients to infection are not clear and are still matter of debate. Interferon gamma is a key cytokine involved namely in the defence against intracellular pathogens. We investigated a possible association of +874 T/A IFNγ polymorphism and infectious complications in sickle cell patients. Seventy-two sickle cell patients were typed for +874 T/A IFNγ polymorphism. Genotype frequencies were different between cases and controls. Indeed, T allele frequency was significantly higher in patients with infections than in patients without infections (χ² = 6.23 ; p = 0.013). Our results suggest that +874 T/A IFNγ polymorphism is associated with infectious complications in sickle cell patients. The T allele could be involved in infections in sickle cell patients.
https://hal.archives-ouvertes.fr/hal-00387081

hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081/document
https://hal.archives-ouvertes.fr/hal-00387081/file/MO_Joannes_et_al._IFNG_polymorphism_and_sickle_cell_disease.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
Some of the immunologic mechanisms involved in malaria physiopathology remain unclear. In animals, the spleen seems to play a key role in protecting the host against malaria. However, little is known about the effect of spleen dysfunction on human malaria. We report two severe cases of Plasmodium falciparum infection with unusual clinical and parasitologic features in two splenectomized men living in French Guiana. The peripheral blood of these cases showed hyperparasitemia, with a high proportion of mature parasites and leukocytes with malaria pigment. Despite appropriate treatment and adequate absorption, hyperparasitemia persisted. Parasite clearance was delayed and one patient died. Only the patient who died had the merozoite surface protein 1 allele B-K1 and the varD gene genotype, which is considered to be a probable parasite virulence factor. These uncommon cases differ from most of those described in the literature, illustrating the complexity of the mechanisms underlying the protective function of the spleen in human malaria.
The American journal of tropical medicine and hygiene

pasteur-00590993
https://hal-riip.archives-ouvertes.fr/pasteur-00590993
PUBMED : 15381808

Éditeur(s) : HAL CCSD
Résumé : International audience
Viral replication in the liver is generally detected by cellular endosomal Toll-like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV-A59 serotype. To address this, C57BL/6 (wild-type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV-A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV-A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3-induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon-β, interleukin-6, tumour necrosis factor-α, CXCL1, CCL2, CXCL10 and alarmin (interleukin-33) than in MHV-A59-infected WT mice and in MHV3-infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3-infected WT mice whereas they were sustained in MHV-A59-infected WT mice and MHV3-infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin-6 induction in comparison to MHV-A59, and depended on viral activation of TLR2 and p38 mitogen-activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3-induced acute fulminant hepatitis. © 2016 John Wiley & Sons Ltd
Immunology

Droits : info:eu-repo/semantics/OpenAccess
hal-01373946
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946/file/Toll-like%20receptor%20%28tlr%29-2%20exacerbates%20murine%20acute%20viral%20hepatitis.pdf
DOI : 10.1111/imm.12627

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
We applied single-molecule photobleaching to investigate the stoichiometry of human Orai1 and Orai3 channels tagged with eGFP and expressed in mammalian cells. Orai1 was detected predominantly as dimers under resting conditions and as tetramers when coexpressed with C-STIM1 to activate Ca(2+) influx. Orai1 was also found to be tetrameric when coexpressed with STIM1 and evaluated following fixation. We show that fixation rapidly causes release of Ca(2+), redistribution of STIM1 to the plasma membrane, and STIM1/Orai1 puncta formation, and may cause the channel to be in the activated state. Consistent with this possibility, Orai1 was found predominantly as a dimer when coexpressed with STIM1 in living cells under resting conditions. We further show that Orai3, like Orai1, is dimeric under resting conditions and is predominantly tetrameric when activated by C-STIM1. Interestingly, a dimeric Orai3 stoichiometry was found both before and during application of 2-aminoethyldiphenyl borate (2-APB) to activate a nonselective cation conductance in its STIM1-independent mode. We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB.
ISSN: 0027-8424

hal-00873833
https://hal.archives-ouvertes.fr/hal-00873833
DOI : 10.1073/pnas.1114814108
PUBMED : 21987805

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
This observation perfectly illustrates the main epidemiological, clinical and biological peculiarities of this parasitic disease. Particularly, as it concerns a tourist who travelled across Africa for a short period of time it is possible to assess the time of exposure to infecting mosquito bites, the maturation period of time as well as the time of clinical incubation. On the other hand the value of the immunological techniques to make the diagnosis of loaiasis as well as the difficulties to treat this affection are stressed upon.
ISSN: 0181-5512

hal-00715439
https://hal.univ-antilles.fr/hal-00715439
PUBMED : 6939746

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
ISSN: 0193-1857

hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/file/102513_1_merged_1499199857-1.pdf
DOI : 10.1152/ajpgi.00436.2016