Bernard Bonnotte

Nicolas Larmonier

Nona Janikashvili

Sylvain Audia

Tinatin Chikovani

BioMed Research International

PubMed

Crossref

EditorialT Lymphocyte Plasticity in Autoimmunity and CancerNona Janikashvili,1 Tinatin Chikovani,2 Sylvain Audia,3Bernard Bonnotte,1,3 and Nicolas Larmonier41 INSERM U1098, Faculty of Medicine, University of Burgundy Franche-Comte´, 21079 Dijon, France2Department of Microbiology and Immunology, Faculty of Medicine, Tbilisi State Medical University, 0117 Tbilisi, Georgia3Department of Internal Medicine and Clinical Immunology, University Hospital of Dijon, 21079 Dijon, France4CNRS UMR 5164, University of Bordeaux, 33076 Bordeaux, FranceCorrespondence should be addressed to Nona Janikashvili; nona.janikashvili@u-bourgogne.frReceived 6 September 2015; Accepted 6 September 2015Copyright © 2015 Nona Janikashvili et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.T lymphocytes are essential for the development and reg-ulation of adaptive immune responses. Upon engagementof their specific antigen receptor in presence of appropriatecostimulatory signals and specific cytokines, naı¨ve CD4+ andCD8+ T cells differentiate into specific effector or suppressorsubsets exhibiting distinct phenotypic characteristics andfunctions. These specialized T lymphocyte subsets are dis-tinguished by a dedicated transcription factor and cytokineexpression profile. Beyond T helper 1 (Th1) and T helper 2(Th2) cells, T helper 9 (Th9), T helper 17 (Th17), T helper22 (Th22), T follicular helper (Tfh), regulatory T cells (Treg),and Type 1 regulatory cells (Tr1) have now been recognized asdistinct subsets into the CD4+ T lymphocyte compartment.Similarly, advances have also been acquired regarding CD8+cell subset diversity (Tc1, Tc2, Tc17, and CD8reg). Althoughsome of these polarized T cell subpopulations remain stableand hardly transdifferentiate into other subsets, evidencehas been provided that others, such as Th17 or Treg cells,display variable degrees of plasticity as demonstrated by theircapability to be “reprogrammed” into different suppressoror proinflammatory effector T cells. T lymphocyte plasticitydepends onmicroenvironmentalmediators such as cytokinesand chemokines which vary in nature and amount during thecourse of autoimmune diseases or the development of cancer.A better understanding of the fundamental mechanisms andthe regulation of T lymphocyte adaptive plasticity is essentialfor a comprehensive characterization of the pathogenesisof immune mediated disorders and cancer immunosurveil-lance. The possibility to interfere with the process of T cellpolarization may also open new therapeutic options.In this special issue, authors addressed topics related tothe altered frequencies and functions of T lymphocyte subsetsand the molecular and cellular mechanisms responsible forT cell lineage commitment, polarization, and reprogrammedadaptive responses in health and pathology. E. Ivanova andA. N. Orekhov provide an overview on the properties of Thelper lymphocyte subsets and describe signaling networks,cytokines, transcription factors, and disturbances which cancause immune dysregulation, such as excessive inflammatoryresponse in autoimmune diseases or enhanced immunetolerance to tumors. T. Caza and S. Landas summarize theepigenetic modifications of cytokine loci that determineCD4+ T cell lineage specifications and emphasize the inter-connected role of the serine-threonine kinase, mammaliantarget of rapamycin (mTOR), and the cellular metabolism inT helper subset polarization.T helper lymphocytes play a key role in promotingspecific anticancer responses and in establishing immunememory. Tumors commonly escape from elimination by theimmune system by using multiple strategies, notably theactive suppression and the modulation of effector immunecells. Impaired effector T cell responses correlate with a poorprognosis in patients with solid tumors. Among numer-ous immune suppressive mechanisms employed by cancer,Hindawi Publishing CorporationBioMed Research InternationalVolume 2015, Article ID 540750, 2 pageshttp://dx.doi.org/10.1155/2015/5407502 BioMed Research Internationalthe deprivation of adenosine triphosphate (ATP) plays animportant role as ATP is essential for T cell activation.Extracellular ATP concentration ismaintained by the ectonu-cleotidase CD39 which is involved in the suppression of Tlymphocyte activation by CD11c+ dendritic cells infiltratingtumors in the mouse lung LLC and mammary 4T1 cancermodels, as described by M. Trad et al.To suppress T effector responses, tumors can promoteTreg expansion and suppressive function which correlateswith a poor prognosis in cancer patients. In human, the IL-7 receptor (CD127) is often used to distinguish CD4+CD25+Treg from activated T cells.The expression of CD127 stronglycorrelates with that of FoxP3, amajor transcription factor thatparticipates to the development and regulatory function ofCD4+CD25+Treg. Treg suppressive functions rely on variousmechanisms involving IL-10 and TGF-𝛽 or cell surface lig-ands. The upregulated expression of TGF-𝛽 complexed withthe latency associated peptide (LAP-TGF-𝛽) on Treg providesan important functional hallmark in this subset. L. Islas-Vazquez et al. investigated the expression levels of LAP-TGF-𝛽 within the CD4+CD25+CD127- Treg subset in patientswith stage IV lung adenocarcinoma. The data indicate thatthe frequencies of LAP-TGF-𝛽+ Treg are elevated and theexpression level of the LAP-TGF-𝛽 complex is significantlyincreased in patients with lung adenocarcinoma. Addition-ally, the authors report that Th17 cells and related cytokinesare increased in smoking subjects and lung adenocarci-noma patients. The results suggest that smoking representan important cause of systemic inflammation, pointing outthe Th17/Treg balance as an important checkpoint in thepathophysiology of lung adenocarcinoma. Complexity ofTh17 responses in the context of tumor is further discussedby L. Guery and S. Hugues. Since the infiltration of tumorsby Th17 is associated with a better outcome, a strategy topromote tumor-induced Treg differentiation toward a Th17phenotype could be a beneficial approach for immunothera-peutic interventions.In the same line, the research article by G. Tejo´n et al.demonstrates that vitamin A restrains the reprogrammingof in vitro generated Treg into IL-17 producing cells in vivoin an adoptive Ag-specific T cell transfer model of mousegut inflammation. The authors additionally report that thepresence of IL-2 during in vitro generation of Treg confersresistance to Th17 conversion and that IL-2 cooperates withretinoic acid (RA) to maintain Foxp3 expression followingstimulation under Th17-polarizing conditions. Of impor-tance, gut microbiome significantly shapes T lymphocytedynamics in an inflammatory condition such as IBD, asextensively reviewed by C. Larmonier et al. Therefore, Th17and Treg stability and plasticity are regulated not only by thesignals they receive during their generation but also by theirlocal microenvironment.The acute phase response also represents an example ofperipheral immune modulation. In the context of systemicinflammation, some proteins, among which is 𝛼1-antitrypsin,exert tolerogenic activities. The topic reviewed by B. Bara-novski et al. underlines that 𝛼1-antitrypsin can indirectlyinhibit T cell responses, by targeting other immune cells. Forinstance, 𝛼1-antitrypsinmaintain the semimature state of DCwhich promotes Treg differentiation. This process appearspivotal during experimental autoimmune encephalomyelitis,rheumatoid arthritis, ulcerative colitis, and type 1 diabetes.AcknowledgmentsWe thank the authors for their valuable contributions to thisspecial issue as well as the reviewers for their constructivecomments to the manuscripts.Nona JanikashviliTinatin ChikovaniSylvain AudiaBernard BonnotteNicolas LarmonierSubmit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

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