Common Chronic Skin T Cell Mediated

Published Date: 02 Nov 2017

multifactorial autoimmune disorder of skin marked by

inflammation, redness and itching. Generally it is found in

teens upto to 20 years of age [1-3]. At the world level approximately

0.3 to 5% population is affected by this disorder

[4]. In Europe it is estimated that 2-3% of the total population

has psoriasis. In Asia and Africa nearly about 1% of the

population is affected with psoriasis [5].

The keratinocyte hyper proliferation in psoriasis may be

due to the activation of T-cells, which produce various inflammatory

mediators like cytokines and adhesion molecules

etc. These mediators are produced via various pathways i.e.,

MAPK/AP-1, JAK–STAT and protein kinase-C (PKCs)

pathways. After T-cell activation, all these mediators induce

a cascade of inflammation, which results in psoriasis. These

entire pathways are unique to psoriasis [6-9]. Psoriatic skin

is rich in inflammatory cells, CD4+, CD8+ T-cell and infiltrating

T-cells express markers such as IL-2 receptors, resulting

in epidermal proliferation and endothelial cell activation

[10, 11]. The exact origin of psoriasis was not well defined

and documented years ago, but now it is very well defined as

several reports show predominance of cytotoxic CD8+

T-cells in psoriatic lesion epidermis, whereas CD4+ cells are

the predominant type in lesional dermis. As per psoriasis

pathology these cells express CD45RO on the surface, indicating

their effectors/memory status [12-14]. Environmental

stress and antigens, cause stimulation of T-cell receptor by

the major histocompatibility complex (MHC I or II) on the

antigen presenting cell (APC). As a result adhesion of T-cell

with the APC, mediated by interaction of surface molecules

such as CD2 on the T-cell with leukocyte function associated

antigen (LFA)-1 on the APC [15] is a another process of

pathogenesis in psoriasis. Signal 1 for psoriasis is ultimately

generated due to over all formation of antigen MHC complexes

with the surface of APCs to interact with T-cell receptors

and CD4/CD8 co-receptors on the surface of T-cells

[12]. Signal 2, is initiated by interactions between CD28 and

CD80, CD40 and CD40L, CD28 and CD86, and LFA3 and

CD2 respectively. Presence of signal 1 and 2 is essential for

T-cell activation [16, 17]. T-cell activation further breaks

down into three steps: 1) activation of T-cell; 2) the migration

of T-cell into the lesion skin; 3) release of cytokines by

activated T-cell in the skin. If anyone of these signal is inhibited,

than T-cell activation ceases. A number of new biological

agents have been developed for psoriasis which inhibit Tcell

activation, for example efalizumab, a humanized anti-

CD11a monoclonal antibody, and alefacept, an LFA-3/IgG1

fusion protein. Activation of CD4+ and CD8+ T-cell, produces

various inflammatory cytokines such as IL-5, IL-4,

and IL-10, IL-2, IFN- _ and TNF-_, which stimulates keratinocytes,

and dendritic cells [18, 19]. The cytokines and

chemokines released in psoriasis lesional skin lead to the

typical epidermal hyperplasia and keratinocyte inflammation.

It is clear from above stated mechanism that psoriasis is

T-cell mediated disease and the activation generates various

cytokines, adhesion molecules and chemokines which as a

result initiates the keratinocyte hyperproliferation and inflammation

in psoriasis.

As compared to normal skin, proliferative epidermal cell

is higher by 26.6% of DNA synthesis in psoriasis. The relative

growth increases from 60 to100% and size of proliferative

cell is doubled. The cell cycle is shortened from 311hr to

36 hrs, which results in decrease in basal cells of stratum

corneum from 27 to 4 days [20, 21]. Conventional treatment

for psoriasis includes topical corticosteroids, tars, anthralin,

vit D analogs, tazarotene and salicylic acids. All of these

have severe side effects like hepatotoxicity. Nephrotoxicity

is associated with methotrexate, cyclosporine etc, teratogenicity

with oral retinoids and skin cancers with

photo/chemotherapy [22, 23]. Modern approach with specific

target action, from biological agents, has fewer side

effects than conventional therapy. Long term use of these

agents has few side effects [24, 25]. According to national

psoriasis foundation survey only 26% of patients were satisfied

with conventional treatment. Recently, a UK survey has

been found that only 44% of patient prefers systemic conventional

treatment than topical treatment [26]. According to

a survey by European federations of psoriasis association, on

17,990 patients only 27% of patients were satisfaction with

conventional treatment. The cause of dissatisfaction among

the masses was due to severe side effect, time consuming

and ineffective therapy which affected their quality of life

[26-28]. Therefore etiology and pathogenesis is very important

for understanding psoriasis. Its mechanism deciphered,

the biomarkers at the cellular and molecular level involved in

mediating inflammatory response and other related responses

during development of psoriasis.

According to the National Institute of Health (NIH),

Biomarkers are indicators of pathogenic process in this disease.

Psoriasis is caused by multi factorial (toxin, stress, microorganism,

etc) or polygenic character, therefore it is essential

to identify the nature of biomarker for effective

treatment of psoriasis [29-33]. NIH classified it into three

types, first type is zero markers that is related to history of

disease, second is, type 1 marker which is related to action of

drug, and the last is type II marker which is associated with

end point i.e. clinical output [32]. From various research

studies it has been found that many markers may act as diagnostic

tool for psoriasis such as oxidative stress, biochemical

factor or enzyme, peptides and gene.