CD28 and colitis: BTNL2 negatively regulates T-cell activation independently of CD28 and CTLA-4 is predominantly expressed in gastrointestinal tissues and is overexpressed in mouse models of colitis.43 Recently, it has been shown that BTNL2 promotes the expression of Foxp3, a transcription factor required for regulatory T-cell development and function.44 Thus, mutations in BTNL2 may affect its ability to regulate T-cell activation in response to mucosal inflammation.