MICA: Targeting of CD1a for treatment of inflammatory skin disease

MICA：靶向 CD1a 治疗炎症性皮肤病

• 批准号: MC_EX_MR/R022550/1
• 负责人: Graham Ogg
• 金额: $ 9.24万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_MR%2FR022550%2F1
• 关键词: MICA; Targeting; CD1a; treatment; inflammatory

Inflammation of the skin is very common, affecting 20-30% of the UK population. Eczema (atopic dermatitis) is amongst the most common, and can associate with asthma, hay-fever and food allergy. Current treatments are suppressive rather than curative, and can carry significant risk of side-effects. There remains a major need for better and safer treatments for eczema and other types of inflammation of the skin, including psoriasis. We have discovered a previously unknown mechanism for skin inflammation to occur, which we have shown is relevant to eczema and other skin conditions. The newly discovered "CD1a" pathway is predominantly relevant to the skin, suggesting that risk of side-effects elsewhere would be minimal. We now wish to progress this knowledge to develop new medicines which can be used to treat skin disease. The MRC/UCB grant award would allow us to identify such potential treatment candidates, and we have all the required facilities and know-how in Oxford to understand which of these would be best to take forward to clinical trials. Overall, by understanding how skin diseases occur, we have been able to open the door to potential new treatments, and we now will develop these towards patient benefit.

皮肤炎症很常见，影响了英国20-30%的人口。湿疹（特应性皮炎）是最常见的，可能与哮喘、花粉热和食物过敏有关。目前的治疗方法是抑制性的，而不是治愈性的，并且有很大的副作用风险。对于湿疹和其他类型的皮肤炎症，包括牛皮癣，仍然需要更好、更安全的治疗方法。我们已经发现了一种以前未知的皮肤炎症发生的机制，我们已经证明了它与湿疹和其他皮肤状况有关。新发现的“CD1a”途径主要与皮肤相关，这表明其他地方的副作用风险将是最小的。我们现在希望在这方面取得进展，以开发可用于治疗皮肤病的新药。MRC/UCB拨款将使我们能够确定这些潜在的治疗候选药物，我们在牛津拥有所有必要的设施和专业知识，可以了解哪些药物最适合进行临床试验。总的来说，通过了解皮肤病是如何发生的，我们已经能够打开潜在的新治疗方法的大门，我们现在将开发这些对患者有益的方法。

项目成果

Natural killer cells get under your skin.

自然杀伤细胞会进入你的皮肤下面。

• DOI: 10.1126/scitranslmed.aba9181
• 发表时间: 2020
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Ogg G

CD1a promotes systemic manifestations of skin inflammation.

• DOI: 10.1038/s41467-022-35071-1
• 发表时间: 2022-12-07
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Hardman, Clare S.;Chen, Yi-Ling;Wegrecki, Marcin;Ng, Soo Weei;Murren, Robert;Mangat, Davinderpreet;Silva, John-Paul;Munro, Rebecca;Chan, Win Yan;O'Dowd, Victoria;Doyle, Carl;Mori, Prashant;Popplewell, Andy;Rossjohn, Jamie;Lightwood, Daniel;Ogg, Graham S.
• 通讯作者: Ogg, Graham S.

CD1a function in human skin disease.

• DOI: 10.1016/j.molimm.2020.12.006
• 发表时间: 2021-03
• 期刊: Molecular immunology
• 影响因子: 3.6
• 作者: de Jong A;Ogg G
• 通讯作者: Ogg G

Developmental cell programs are co-opted in inflammatory skin disease.

• DOI: 10.1126/science.aba6500
• 发表时间: 2021-01-22
• 期刊: Science (New York, N.Y.)
• 作者: Reynolds G;Vegh P;Fletcher J;Poyner EFM;Stephenson E;Goh I;Botting RA;Huang N;Olabi B;Dubois A;Dixon D;Green K;Maunder D;Engelbert J;Efremova M;Polański K;Jardine L;Jones C;Ness T;Horsfall D;McGrath J;Carey C;Popescu DM;Webb S;Wang XN;Sayer B;Park JE;Negri VA;Belokhvostova D;Lynch MD;McDonald D;Filby A;Hagai T;Meyer KB;Husain A;Coxhead J;Vento-Tormo R;Behjati S;Lisgo S;Villani AC;Bacardit J;Jones PH;O'Toole EA;Ogg GS;Rajan N;Reynolds NJ;Teichmann SA;Watt FM;Haniffa M
• 通讯作者: Haniffa M