scholarly journals CX3CL1 (fractalkine) and its receptor CX3CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin

2014 ◽  
Vol 211 (6) ◽  
pp. 1185-1196 ◽  
Author(s):  
Delphine Staumont-Sallé ◽  
Sébastien Fleury ◽  
Anne Lazzari ◽  
Olivier Molendi-Coste ◽  
Nicolas Hornez ◽  
...  

Atopic dermatitis (AD) is a chronic allergic dermatosis characterized by epidermal thickening and dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Among chemokines and chemokine receptors associated with inflammation, increased levels of CX3CL1 (fractalkine) and its unique receptor, CX3CR1, have been observed in human AD. We have thus investigated their role and mechanism of action in experimental models of AD and psoriasis. AD pathology and immune responses, but not psoriasis, were profoundly decreased in CX3CR1-deficient mice and upon blocking CX3CL1–CX3CR1 interactions in wild-type mice. CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD. Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4+ T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4+ T cell retention in inflamed skin, indicating a new function for this chemokine receptor. Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.

Cell Reports ◽  
2021 ◽  
Vol 35 (4) ◽  
pp. 109038
Author(s):  
Guorui Xie ◽  
Xiaoyu Luo ◽  
Tongcui Ma ◽  
Julie Frouard ◽  
Jason Neidleman ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1120
Author(s):  
Dae Woon Choi ◽  
Sun Young Jung ◽  
Gun-Dong Kim ◽  
So-Young Lee ◽  
Hee Soon Shin

Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.


2003 ◽  
Vol 34 (1) ◽  
pp. 114-116 ◽  
Author(s):  
Jacques Reynes ◽  
Vincent Baillat ◽  
Pierre Portales ◽  
Jacques Clot ◽  
Pierre Corbeau
Keyword(s):  
T Cell ◽  

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