T helper 17 cells: discovery, function, and physiological trigger

Abstract

In the few years since their discovery, T helper 17 cells (T(H)17) have been shown to play an important role in host defense against infections, and in tissue inflammation during autoimmunity. T(H)17 cells produce IL-17, IL-21, IL-10, and IL-22 cytokines, and thus have broad effects on a variety of tissues. Notably, the requirement for the immunosuppressive cytokine TGF-beta along with the pro-inflammatory cytokine IL-6 for T(H)17 differentiation supports the intimate relationship between the T(H)17 subset and FOXP3(+) regulatory T cells. Here, we discuss current knowledge on effector functions and differentiation of the T(H)17 lineage. Furthermore, we now know of a physiological stimulus for T(H)17 differentiation: innate immune recognition of cells undergoing apoptosis as a direct result of infection induces unique development of this subset. As our knowledge of T(H)17 and T regulatory cells grows, we are building on a new framework for the understanding of effector T cell differentiation and the biology of CD4(+) T cell adaptive immune responses.

Increased muscle expression of interleukin-17 in Duchenne muscular dystrophy

“…24 However, this single observation is in apparent contradiction with a vast body of evidence supporting a major role of IL-17 in several models of chronic autoimmune inflammation, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveoretinitis. 8,22,[25][26][27][28][29][30][31][32] We did not find any detectable levels of IL-17 in control muscles. Consistent with the abovementioned observations in JDM, IL-17 mRNA was detectable in all except 2 JDM muscle biopsy samples tested, albeit with a wide range of expression levels.…”

“…[7][8][9][10][11][12][13] Production of IL-17 characterizes proinflammatory T helper 17 lymphocytes (Th17) and innate immune cells. 7,8 Th17 have been shown to have a reciprocal developmental pathway and opposing effects in the immune response from regulatory T cells (Treg), 8,14,15 , whose master gene is the transcription factor Forkhead box P3 (Foxp3). 16 -18 A fine balance between Th17 and Treg is believed to be crucial for tissue immune homeostasis.…”

Follistatin: A Novel Therapeutic for the Improvement of Muscle Regeneration

“…IL17a is described as a proinflammatory cytokine that is produced by a subset of T cells known as helper T 17 cells (Torchinsky and Blander, 2010). IL17a has been found to be upregulated in Duchenne muscular dystrophy and has been demonstrated to negatively affect myoblast migration and terminal differentiation (De Pasquale et al, 2012;Kocic et al, 2013).…”

Immunological changes of T helper cells in flow cytometer‑sorted CD4+ T cells from patients with Hashimoto's thyroiditis

“…A relatively newly discovered subset of T helper cells, Th17, that primarily produce IL-17 may be involved not only in the defense against certain pathogens but also in driving inflammation and autoimmunity (7). Another subset of CD4 + T cells, Th3 lymphocytes, predominantly synthesize tumor growth factor-β and are considered as regulatory cells (8).…”