Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 139

T H17 Cell

T H17 cells are involved in host defense against specific pathogens, in tumor
immunology, autoimmunity, and tissue inflammation. They interact with regulatory
T cells to prevent tissue inflammation and mediate self-tolerance.
Transcription factors Activator protein AP1, STAT3, and retinoic acid-related
orphan receptors ROR

T or NR1f3-2) promote
the generation of T H17 cells. Production of IL17 relies on ROR

α (or NR1f1) and ROR γ 2(ROR γ

2. The STAT3
factor activated by IL6, IL21, and IL23 binds to Il17 and Il21 loci and regulates
the expression of IL23 receptor, ROR

γ

2. 121
Differentiation of naive T cells into T H17 and T Reg cells depends on the local
cytokine environment and antigen-presenting cells. Differentiation of T H17 cell is
induced by transcription factor ROR

α ,andROR γ

2 in collaboration with STAT3 in response
to the combined effect of IL6, IL23, and TGF

γ

. The transcription factor forkhead
box-P3 can hinder NR1f3-2 activity. The development and functioning of FOxP3

β

+
T Reg cells require the cooperation of FoxP3 and nuclear factor of activated T cells
(NFAT) to regulate FoxP3 target genes. 122 T H17 cells also express CCR6 receptor.
Differentiation into T H17 cells can occur in the absence of TGF β [ 255 ].

Interleukin-6 and -23 in combination with IL1 cause IL17 production in naive pre-

cursors. Therefore, T H17 cells constitute diverse subpopulations, such as TBx21

β

+ ,

ROR ,T H17 cells.

Basic leucine zipper ATF-like transcription factor (BATF), or B-cell-activating
transcription factor (BATF), that contains only a basic region and leucine zipper
domain (and not transcriptional activation domains of Activator protein-1) 123
is involved in the differentiation of T H17 cells [ 256 ]. The BATF factor binds
conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and
Il22 promoters. 124
T H17

γ 2 +

cells synthesize several cytokines, such as IL2, IL17, granulocyte-

macrophage colony-stimulating factor (CSF2), interferon- , and tumor-necrosis

factor in the human tumor environment for tumor eradication [ 257 ]. 125 On the other
hand, tumor-infiltrating T Reg cells suppress T H17 -cell expansion in tumors.

γ

121 The Il17 locus is composed of Il17A and Il17F genes. Encoded IL17a and IL17f can form
homo- and heterodimers.
122 Most (but not all) FoxP3

+ T Reg cells express IL2R α (CD25). A subset of CD25 + (IL2R α+ )

T cells comprises FOxP3 effector T cells without T Reg function. Calcium ions are needed for

nuclear translocation of NFAT and cytokine production. Stromal interaction molecules StIM1 and
StIM2 detect intracellular calcium storage depletion and activate calcium release-activated calcium
channels for calcium entry.
123 Early response transcription factor Activator protein-1 is a dimer of Jun, Fos, Maf, Jun
dimerization protein (JDP), and activating transcription factor family members (ATF1-ATF7).
124 Factor BATF is also expressed in T H1 and T H2 cells, but it is not required for T H2 development.
125 Interleukin-17, or IL17a, also called cytotoxic T-lymphocyte-associated protein CTLA8, be-
longs to a the IL17 family with IL17b to IL17f.

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