A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17

Nat Immunol. 2005 (11):1133-41

Speaker： 李羽涵                                 Time：2005/11/23 15:10-16:00

Commentator： 黎煥耀 老師                        Place：Room 601

Abstract:

CD4 T helper (T_H) cells are essential regulator of immune responses and inflammatory diseases. IL-17 (also called IL-17A) has been associated with

many inflammatory diseases such as rheumatoid arthritis, asthma, lupus and allograft rejection. Many in vitro studies have indicated a proinflammatory

function for IL-17. IL-17 expression is generally thought to be restricted to T cells. In humans, IL-17 is expressed by activated CD4 T cells and by T_H1 and

T_H0 cells but not by T_H2 cells, whereas in mice, IL-17 expression is strongly induced by IL-23 in memory T cells. The authors evaluated in vitro and in vivo

the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. The generation of IL-17-producing CD4⁺ T

cells (T_H-17) following immunization with antigen was impaired in mice that were deficient in B7 or inducible T-cell co-stimulator (ICOS), indicating this

process required the co-stimulatory molecules CD28 and ICOS. They also revealed that the differentiation of T_H-17 cells occurred efficiently independent of

the cytokines and transcription factors required for T_H1 or T_H2 cells differentiations. Further, they used an animal model to show that in vivo, IL-17

potently regulated chemokine expression by tissue cells, and IL-17 overexpression in the lung caused airway inflammation. In contrast, IL-17-specific

inhibition attenuated immune infiltration in the brain in an experimental autoimmune encephalomyelitis (EAE) model. Taken together, they demonstrated that

T_H-17 cells were a completely separate and early lineage of effector CD4⁺ T_H cells produced directly from naive CD4 T cells and IL-17 had a critical

function during immune and autoimmune response. Further research on this subset of T_H cells should demonstrate greater complexity of T_H cells regulation

and function in immune response.

References

1.     Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., Dong C. 2005. A distinct lineage of CD4

T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 6(11):1133-41.

2.     Kolls, J.K., Linden, A. 2004. Interleukin-17 family members and inflammation. Immunity 21, 467-476.