Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 56

Tabl e 3. 2. Cytokines in immunity and hematopoiesis. Erythropoietin, thrombopoietin, growth
hormone, and prolactin have structures and signaling mechanisms similar to those of interleukins
and colony-stimulating factors, referred to as type-1 cytokines. Interferons are type-2 cytokines.
Many cytokines are pleiotropic. Different cytokines have overlapping activities (TGF β : transform-

inggrowthfactor- β ;TNF α : tumor-necrosis factor- α ).

Immunity Hematopoiesis

Interleukins Interleukins

TGF β Colony stimulating factors

Interferons
TNF α

Chemokines

Moreover, cytokines can signal via several types of receptors and several cytokine
types can bind to given receptors. Also, cytokine receptors have common structural
components. 7 Cytokines are downregulated by cytokine antagonists.
After enzymatic cleavage of the extracellular domain of cytokine receptors,
soluble cytokine receptor fragments in blood and extracellular fluid can bind to
cytokines, thereby neutralizing their activity.
Most cytokine receptors, as well as growth hormone 8 and prolactin receptors of
the immune and hematopoietic systems belong to the family of class-1 cytokine
receptors. Most class-1 cytokine receptors are dimers, with a cytokine-specific and
a signal-transducing subunit, which is usually not specific for the cytokine. Certain
receptors are trimers.
Class-1 cytokine receptors are subdivided into subsets composed of recep-
tors with identical signal-transducing subunits: (1) granulocyte-monocyte colony-
stimulating factor (gmCSF) subset includes the receptors for IL3, IL5, and CSF2;
(2) IL6 subset comprises the receptors for IL6, IL11, and IL12; and (3) IL2 subset
encompasses the receptors for IL2, IL4, IL7, IL9, and IL15.
Ligands for class-2 cytokine receptors are interferons Ifn .

The TNF receptor family includes TNF receptor-1 (TNFR1 or TNFRSF1a), TNF
receptor-2 (TNFR2 or TNFRSF1b), TNFRSF5, and TNFRSF6a, among numerous

α , Ifn β , and Ifn γ

7 Interleukins IL3 and IL5, as well as granulocyte-monocyte colony-stimulating factor (gmCSF
or CSF2) share a common cytokine receptor β c chain (IL3R β ). Receptors of IL6, IL11,
leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), novel
neurotrophin-1 (NNT1), a.k.a. B-cell-stimulating factor-3 (BSF3) and cardiotrophin-like cytokine
(CLC), and cardiotrophin-1 (CT1) share the GP130 signal-transducing molecule. Interleukins IL2,
IL4, IL7, IL9, IL15, and IL21 share the common cytokine receptor γ chain (IL2R γ ); IL12 and

IL23, the IL12R β 1 chain; IL4 and IL13, the type-2 IL4 receptor (IL4R α ); and IL7 and TSLP, the

IL7R receptor subunit [ 98 ].

8 The growth hormone is a type-1 cytokine. It acts via the JaK-STAT pathway, which mediates
activation of STAT transcription factors and the Ras-MAPK pathway for phosphorylation of ELk1
transcription factor.

α