Th1/Th2 cells in inflammatory disease states: therapeutic implications

Moss, Ronald B.; Moll, Thomas; El-Kalay, Mohammad; Kohne, Connie; Hoo, William Soo; Encinas, Jeffrey; Carlo, Dennis J.

doi:10.1517/14712598.4.12.1887

Cited by 85 publications

(57 citation statements)

References 58 publications

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“…The polarization of Th cells into either Th1 or Th2 is regulated, respectively, by IL-12 (Il12), which activates Stat4 (Jacobson et al, 1995;Thierfelder et al, 1996), and IL-4/IL-13 (Il4/Il13), which activate Stat6 (Kaplan et al, 1996). Disruption in the developmental control of Th1 and Th2 cells has been associated with diseases such as asthma, autoimmunity and cancer (Chatila, 2004;Moss et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development

et al. 2007

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Naïve T helper cells differentiate into Th1 and Th2 subsets, which have unique cytokine signatures, activators and transcriptional targets. The Th1/Th2 cytokine milieu is a key paradigm in lineage commitment, and IL-4 (Il4), IL-13 (Il13) and Stat6 are important mediators of Th2 development. We show here, for the first time, that this paradigm applies also to mammary epithelial cells, which undergo a switch from Th1 to Th2 cytokine production upon the induction of differentiation. Thus, the Th1 cytokines IL-12 (Il12), interferon gamma (INF␥; also known as Ifng) and Tnf␣ are downregulated concomitantly with the upregulation of the Th2 cytokines IL-4, IL-13 and IL-5 (Il5) as epithelial cells commit to the luminal lineage. Moreover, we show that Th2 cytokines play a crucial role in mammary gland development in vivo, because differentiation and alveolar morphogenesis are reduced in both Stat6 and IL-4/IL-13 doubly deficient mice during pregnancy. This unexpected discovery demonstrates a role for immune cell cytokines in epithelial cell fate and function, and adds an unexpected tier of complexity to the previously held paradigm that steroid and peptide hormones are the primary regulators of mammary gland development.

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Section: Introductionmentioning

confidence: 99%

The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development

et al. 2007

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“…Key regulators of this response are a subset of T cells called CD4-positive T helper (Th) cells, which can be further differentiated into two subtypes, Th1 and Th2 cells, by the different cytokines they produce (2). The appropriate regulation of Th cell immunity is critical in the control and prevention of diverse diseases.…”

Section: Introductionmentioning

confidence: 99%

Increased T-helper interferon-γ-secreting cells in obese children

Pacifico

Renzo²,

Anania³

et al. 2006

eur j endocrinol

165

115

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Objective: Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features. Study design: In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-g or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning. Results: Geometric mean percentages of IL-2-and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-g was significantly higher in the obese than in the control (P , 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-g-positive cells was positively associated with leptin (P ¼ 0.002), insulin (P , 0.00 005), and HOMA-IR values (P , 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-g-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P ¼ 0.001), but not with body mass index-standard deviation score and total body fat mass. Conclusions: In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-g is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.European Journal of Endocrinology 154 691-697

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“…Одночасно з цим зроста-ла концентрація прозапального ІЛ-17, який стимулює продукцію багатьох цитокінів, у тому числі і ІЛ-1. Такий дисбаланс у вмісті про-та протизапальних цитокінів у групі тварин із ХХН є характерним для зрушень у системі Т-клітинної імунної відповіді, що свідчить про розвиток хронічного запалення [10]. При цьому збільшувався вміст RANKL у сироватці крові і його природного антагоніста остеопротегерину.…”

Section: результати та їх обговоренняunclassified