TY  - JOUR
A1  - Kader, Hidaya A.
A1  - Azeem, Muhammad
A1  - Jwayed, Suhib A.
A1  - Al-Shehhi, Aaesha
A1  - Tabassum, Attia
A1  - Ayoub, Mohammed Akli
A1  - Hetta, Helal F.
A1  - Waheed, Yasir
A1  - Iratni, Rabah
A1  - Al-Dhaheri, Ahmed
A1  - Muhammad, Khalid
T1  - Current insights into immunology and novel therapeutics of atopic dermatitis
JF  - Cells
N2  - Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.
KW  - atopic dermatitis
KW  - immune system
KW  - T cells
KW  - B cells
KW  - keratinocytes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241008
SN  - 2073-4409
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Rauschenberger, Tabea
A1  - Schmitt, Viola
A1  - Azeem, Muhammad
A1  - Klein-Hessling, Stefan
A1  - Murti, Krisna
A1  - Grän, Franziska
A1  - Goebeler, Matthias
A1  - Kerstan, Andreas
A1  - Klein, Matthias
A1  - Bopp, Tobias
A1  - Serfling, Edgar
A1  - Muhammad, Khalid
T1  - T cells control chemokine secretion by keratinocytes
JF  - Frontiers in Immunology
N2  - The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.
KW  - chemokine
KW  - keratinocytes
KW  - IFN
KW  - lichen planus
KW  - T cells
KW  - Nfatc1
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195695
SN  - 1664-3224
VL  - 10
IS  - 1917
ER  -