Newest member of the T helper cell family: Th17

TH17 cells produce IL-17, IL-6, TNF, and IL-22. TH17 cells are important for neutrophil recruitment and they contribute to autoimmune disorders.

After activation by cytokines, CD4(+) naive T cells differentiate into lineages of helper/effector (T(H)) and regulatory T (Treg) cells. The trusted binary system of T(H)1 and T(H)2 has been expanded to include the IL-17-producing T(H)17 cell lineage, which plays a role in immune responses to infectious agents and autoimmune diseases.

T(H)17 cells are the newest member of the T(H) cell family and are characterized by their ability to produce cytokines such as:

- IL-17
- IL-17F
- IL-22
- CCL20

T(H)17 cells contribute to host defense as effector cells that protect against extracellular bacteria. Their activities, however, are also pivotal in autoimmune diseases.

T(H)17 cells are also associated with the development of:

- allergic contact dermatitis
- atopic dermatitis
- asthma


Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing antibodies. Image source: Wikipedia, Mikael Häggström, public domain.

T(H)1 cells produce IFN-gamma and are involved in cell-mediated immunity. T(H)2 cells produce IL-4 and contribute to humoral immunity.

Acting as counter-balance, Treg cells maintain peripheral tolerance and protect the host from auto-aggressive lymphocytes. Forkhead box protein 3-positive (FOXP3(+)) Treg cells secrete TGF-beta and IL-10 and downregulate effector T cells.

T(H)17 cells generate IL-17 and play an important role in immune responses to fungi and extracellular pathogens.

Anti-IL-17 Receptor Antibody Brodalumab Helps Patients with Psoriasis - NEJM, 2012. Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.

Autosomal dominant hyper-IgE syndrome, a rare primary immunodeficiency disorder, is caused by mutations of signal transducer and activator of transcription 3 (STAT3), preventing T(H)17 lineage differentiation and increasing susceptibility to Staphylococcus and Candida species infections.

Mutations in the FOXP3 gene interfere with Treg cell development and cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).

Lymphoid tissue inducer-like cells and natural killer-like cells, termed RORgammat(+)NKp46(+) or NK-22 cells, might also play a role in allergic diseases because of their propensity to produce IL-17 and IL-22.

Which cytokines promote neutrophil tissue inflammation?

(A) IL-2

(B) IL-5

(C) IL-8

(D) IL-10

(E) IL-17

Answers: IL-8 and IL-17.

References

Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Interleukin-17 levels related to severity of allergic rhinitis
Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.

Sarcoidosis is a Th1/Th17 multisystem disorder, Thorax 2011.