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Chapter 11:: Cytokines:: Ifor R. Williams & Thomas S. Kupper
Chapter 11:: Cytokines:: Ifor R. Williams & Thomas S. Kupper
CLASSIFICATIONS OF CYTOKINES
The first cytokines described had distinct and easily recognizable biological activities,
exemplified by IL-1, IL-2, and the interferons (IFNs). The term cytokine was first coined by
Cohen in 1975, to describe several such activities released into the supernatant of an
epithelial cell line.2 Prior to this, such activities had been thought to be the exclusive domain
of lymphocytes (lymphokines) and monocytes (monokines) and were considered a function
of the immune system. Keratinocyte cytokines were first discovered in 1981,3 and the list of
cytokines produced by this epithelial cell rivals nearly any other cell type in the body.4,5 The
number of molecules that can be legitimately termed cytokines continues to expand and has
brought under the cytokine rubric molecules with a broad range of distinct biological
activities. The progress in genomic approaches has led to identification of novel cytokine
genes based on homologies to known cytokine genes. Making sense of this plethora of
mediators is more of a challenge than ever, and strategies to simplify the analysis of the
cytokine universe are sorely needed.
NOVEL INTERLEU KIN 10-RELATE D CYTOKINE S: INTERLEUKINS 19, 20, 22, 24,
AND 26
A series of cytokines related to IL-10 have been identified and shown to engage a number of
receptor complexes with shared chains.40 IL-19, IL-20, and IL-24 transmit signals via a
complex consisting of IL-20Rα and IL-20Rβ. IL-22 signals through a receptor consisting of
IL-22R and IL-10Rβ. The receptors for these IL-20 family cytokines are preferentially
expressed on epithelial cells including keratinocytes. Increased expression of these cytokines
and their receptors is associated with psoriasis. The IL-20 family cytokines have profound
effects on the proliferation and differentiation of human keratinocytes in culture.41
Transgenic mice overexpressing IL-20, IL-22, or IL-24 develop epidermal hyperplasia and
abnormal keratinocyte differentiation. 42 All of these findings point to a significant role
for these cytokines in the epidermal changes associated with cutaneous inflammation. T cells
producing IL-22 that elaborate a distinct set of cytokines from Th1, Th2 and Th17 cells have
been isolated from the epidermis of patients with psoriasis and other inflammatory skin
disorders. The IL-22 produced by these T cells promotes keratinocyte proliferation and
epidermal acanthosis.43,44
KEY REFERENCES
Full reference list available at www.DIGM8.com
DVD contains references and additional content
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3. Luger TA et al: Epidermal cell (keratinocyte)-derived thymocyte-activating factor
(ETAF).J Immunol 127:1493, 1981
4. Kupper TS: The activated keratinocyte: A model for inducible cytokine production by non
bone marrow-derived cells in cutaneous inflammatory and immune responses. J Invest
Dermatol 94:146S, 1990
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27. Ziegler SF, Artis D: Sensing the outside world: TSLP regulates barrier immunity. Nat
Immunol 11:289, 2010
35. Griffiths CE et al: Comparison of ustekinumab and etanercept for moderate-to-severe
psoriasis. N Engl J Med 362:118, 2010
43. Eyerich S et al: Th22 cells represent a distinct human T cell subset involved in epidermal
immunity and remodeling. J Clin Invest 119:3573, 2009
44. Fujita H et al: Human Langerhans cells induce distinct IL-22-producing CD4+ T cells
lacking IL-17 production. Proc Natl Acad Sci U S A 106:21795, 2009