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Th17 Cells: Deciphering the T Helper Cell Paradigm


A New T Cell Lineage


CD4+ T helper cells are critical mediators of the cellular immune response. For many years, due to cytokine expression patterns, it was thought that CD4+ T helper cells existed as a dichotomy of lineages named Th1 and Th2. However, as these subsets were analyzed more closely, it became apparent that the T helper cell population was not limited to these two subsets. Although it has long been appreciated that IL-17 (also known as IL-17A) production by T cells is required for protection against some pathogens, in 2000 it was demonstrated that IL-17A was produced by a unique subset of T helper cells. Subsequently, it was definitively shown that T cells could differentiate into IL-17-producing cells in vitro and in vivo independently of Th1 or Th2 cell development thereby establishing Th17 cells as a unique T helper cell lineage. Functionally, Th17 cells play a role in host defense against extracellular pathogens by mediating the recruitment of neutrophils and macrophages to infected tissues. Moreover, it is becoming evident that aberrant regulation of Th17 cells may play a significant role in the pathogenesis of multiple inflammatory and autoimmune disorders. Differentiation of Th17 cells is controlled by a “master-regulator” transcription factor, RORγt, which directs a specific and heritable gene expression profile. RORγt was initially identified as a thymus-specific isoform of RORγ, and later, it was discovered that RORγt is also expressed in Th17 cells. RORγt deficiency results in diminished Th17 activity and severely reduced expression of IL-17.

Th17 Differentiation



eBioscience Provides a Complete Solution for Th17 Analysis


eBioscience offers a comprehensive portfolio of reagents for the study of Th17 cells by flow cytometry, immunoassay and bioassay. Our product introductions include the first antibody for flow cytometric detection of the Th17 “master-regulator” RORγ(t) and the first heterodimer-specific ELISA sets for the detection of both mouse and human IL-17AF. eBioscience continues to provide high-quality reagents to unravel the derivation and function the Th17 lineage through analysis of cytokines as well as proteins expressed in the nucleus and on the cell surface. The recent introduction of the FlowCytomix™ platform enables the flow cytometric detection of multiple cytokine analytes providing you with yet another tool for Th17 cell analysis.


NEW Th17 Products from eBioscience!


Mouse Th17 Biology

Human Th17 Biology

Properties of T Helper Lineages
Feature Th1 Th2 Th9 Th17 Th22 Treg Tfh
Surface Expression IL-12RB2, IFNγR, Tim3 IL-17RB, Tim1 -- IL-1R1, IL-12RB1, IL-23R, CCR6 (h), CD161 (h), IL-13Rα1 PDGFR, CCR10 CD25, CD39, CD73, CD101, CD127lo, FR4 (m), GITR/AITR CD84, CXCR5, IL-6R, IL-21R, gp130
Unique Cytokine Expression IFNγ IL-4, IL-5, IL-13 IL-9 IL-17A, IL-17F, IL-17AF, IL-21, IL-22 IL-22, TNFα TGFβ IL-6
"Master-Regulator" Transcription Factor T-bet Gata-3 -- RORγt -- Foxp3 BCL6
STAT Regulators STAT1, 4 STAT6 -- STAT3 -- STAT5 STAT3
Polarizing Cytokines IL-12, IFNγ, IL-27 IL-4, IL-25 IL-4, TGFβ IL-6, TGFβ, IL-21 TNFα, IL-6 TGFβ IL-6, IL-21, CXCL13


References


Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008 May;8(5):337-48. Review.

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005 Nov;6(11):1123-32.

Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006 Sep 22;126(6):1121-33.


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