Table 2.

Roles of islet‐expressed chemokines in type 1 diabetes

Receptor	Ligands	Ligand expression in islets		Role in T1D
		Animal models	Human
CCR2	CCL2	Mid 4	Mid 60, 102, 109	NOD and C57Bl/6 T1D models show contradictory outcomes CCR2–/– NOD mice have impaired T1D progression 69 Transgenic expression of CCL2 in the islets of C57Bl/6 mice induced T1D penetrance 70 Transgenic expression of CCL2 in the islets of NOD mice reduces T1D penetrance 71
CCR5	CCL3,	Mid 63	Low/neg 60	CCR5–/– NOD mice have accelerated T1D 69 CCL3–/– NOD mice have impaired T1D progression 72
	CCL4,	Mid 63	Low/neg 60
	CCL5	Mid 55	Mid 55
CCR7	CCL19,	Mid 110		CCR7–/– NOD mice do not progress to T1D 79
	CCL21	Mid 110
CXCR3	CXCL9,	Mid 13, 55, 57	Mid 55, 60	NOD and C57Bl/6 T1D models show contradictory outcomes CXCL10 neutralizing antibody can delay and reverse T1D in NOD mice 65, 83 Transgenic CXCL10 expression in C57Bl/6 islets can drive islet infiltration 84 Virally induced T1D in C57Bl/6 is impaired when T cells lack CXCR3 82 CXCR3–/– NOD mice get accelerated T1D 66 CXCR3 deficient T cells are able traffic effectively to infiltrated islets in NOD mice 13
	CXCL10	High 13, 55, 57, 64, 82	High 55, 60
CXCR4	CXCL12	Mid 89, 90, 91	Mid 60	Blockade of CXCL12 in short‐term disease transfer leads to accelerated disease 89. Long‐term blockade of CXCL12 reduces T1D progression in NOD mice 90
CXCR5	CXCL13	Mid 25, 111		Transgenic expression of CXCL13 in islets drives islet infiltration in C57Bl/6 mice 97 Antibody blockade of CXCL13 disrupts tertiary lymphoid organization in the islets in NOD mice 25
CXCR6	CXCL16	High 13		CXCL16 is highly expressed in islet myeloid cells in NOD mice 13 CXCR6 deficient T cells traffic to islets normally in NOD and C57Bl/6 13 CXCR6 is located within the IDDM22 T1D risk locus in human 94, 95 CXCL16 is a candidate gene for the Idd4 T1D risk locus in mouse 93
M3 viral decoy receptor	CC chemokine ligands			Islet expression of M3 blocks T1D progression in NOD mice 63

CCR = chemokine receptor; CCL = CC chemokine ligand; NOD = non‐obese diabetic; T1D = type 1 diabetes; CXCR = C‐X‐C chemokine receptor; CXCL = C‐X‐C motif) ligand 1; Idd = insulin‐dependent diabetes.