Th17 Cells

Th17 Cells - 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 has become evident that aberrant regulation of Th17 cells may play a significant role in the pathogenesis of multiple inflammatory and autoimmune disorders.

Th17 Cells

Differentiation of Th17 cells is controlled by a “master-regulator” transcription factor, ROR gamma t, which directs a specific and heritable gene expression profile. ROR gamma t was initially identified as a thymus-specific isoform of ROR gamma, and later, it was discovered that ROR gamma t is also expressed in Th17 cells. ROR gamma t deficiency results in diminished Th17 activity and severely reduced expression of IL-17.

Th17 Cell Lineage Diagram

Th17 Cell Lineage

 

Properties of T Cell Helper Lineages
FeatureTh1Th2Th9Th17Th22TregTfh
Surface Expression

IL-12RB2

IFN gamma R

Tim3

IL-17RB

Tim1

 --

IL-1R1

IL-12RB

IL-23R

CCR6

CD161

IL-13Ra1

PDGFR

CCR10

CD25

CD39

CD73

CD101

CD127lo

FR4

GITR / AITR

CD84

CXCR5

IL-6R

IL-21R

gp130

Unique Cytokine Expression IFN gamma

IL-4

IL-5

IL-13

IL-9

IL-17A

IL-17F

IL-17AF

IL-21

IL-22

IL-22

TNF alpha

TGF beta

 

IL-6

Master Regulator Transcription Factor T-bet Gata-3 -- ROR gamma t -- Foxp3 BCL6
STAT Regulators

STAT1

STAT4

STAT6 -- STAT3 -- STAT5 STAT3
Polarizing Cytokines

IL-12

IFN gamma

IL-27

IL-4

IL-25

IL-4

TGF beta

IL-6

TGF beta

IL-21

TNF alpha

IL-6

TGF beta

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.