Table 1.

Immune phenotypes in clock-specific global and conditional knockout systems.

Clock gene	Model	Effect	Tissue/cells	Reference
Bmal1	KO	Impaired B cell development, reduced B cell numbers Accelerated aging with increased risk for arthropathy	Blood, spleen	[41]
	Chimera	Leishmania infection: -Loss of time-dependent infection extent -Loss of time-dependent neutrophil and macrophage infiltration -Loss of time-dependent rhythmic chemokine expression	Neutrophils, peritoneal macrophages	[88]
	Lyz2-Cre	Reduced survival after LPS	Macrophages	[44]
		Reduced survival after Listeria infection	Monocytes	[31]
		Increased proinflammatory state after LPS:	Macrophages
		-Increased IL-6		[28]
		-Increased TNFa, reduced Il10		[44]
		-Increased ROS, HIF1α, Il6, Il1b		[45]
		Increased proinflammatory cytokines after L. monocytogenes infection	Monocytes	[31]
		Increased proinflammatory miR-155 cluster	Macrophages	[44]
		Higher phospho-p65
		Increased inflammatory state in diseases:
		-Allergic asthma	Eosinophils	[46]
		-EAE (increased IM infiltration, increased IL-1β)	CNS	[47]
	hMRP8-cre	Impaired clearance of aged neutrophils	Neutrophils	[22]
	Cd4-cre	Impeded LN homing Loss of lymph and LN half-life diurnal oscillation	T cells	[27]
	Cd19-cre	Loss of oscillations in lymph and LN	B cells	[27]
	Rorgt-cre	Reduced small intestinal lamina propria (siLP) ILC3s	siLP ILC3	[89,90]
		Reduced epithelial reactivity	Small intestine
		Increased infection with Citrobacter rodentium
Clock	KO	Reduced NFκB activity	Hepatocytes, MEFs	[55]
	Δ19 mutant	Reduced inflammatory cytokines after LPS, TNFα	MEFs	[42]
		Reduced Il6, Il1b, Cxcl1, Ifnb, & Ccl2 after inflammatory stimuli	Macrophages (BMDMs)	[56]
	Δ19 mutant chimera with W/Wv mice	Loss of IgE-mediated degranulation and mast cell signaling	Mast cells	[91]
		Loss of FcεRIβ oscillation
Per1	KO	Increased TNFα, IL-1β, IL-6, & MCP-1 after LPS	Macrophages	[57]
Per2	KO	Reduced IFNγ, IL-1β after LPS	Plasma	[58]
		Resistant to septic shock
	Per2-Brdm1	Reduced TNFα, IL-12 after CpG	Macrophages	[37]
		Increased IL-6 after LTA, loss of IL-6 rhythm	Macrophages	[60]
		Loss of diurnal anaphylactic cutaneous reaction	Mast cells (skin, BM)	[61]
Cry1	KO	Increased IL-6	Fibroblasts	[64]
Cry1/2	KO	Increased T cell cellularity	MEFs, Splenocytes	[63]
		Increased TNFα
		Increased IL-6, Cxcl1, iNOS, constant NFκB activity	Hypothalamus, Fibroblasts, Macrophages	[64]
		Increased LPS hypersensitivity
		Spontaneous autoimmune disease:
		Increased IgG and IgM	Serum, lung, kidney	[65]
		Increased IL-1β, IL-6, MMP-3, & TNFα in arthritis	Serum
Rev-Erbα	Agonist	Reduced Il-6, Cxcl11, Ccl2, Cxcl6, & Il19	Macrophages	[28]
	KO	Loss of diurnal LPS response	Macrophages	[64]
		Increased Cx3cr1 & Mmp9		[66]
		Reduced NKp46+ siLP ILC3s	siLP ILC3s	[92]
		Increased DN and CCR6+ siLP ILC3s
	Ccsp-Rev-Erbα-DBDm	Increased neutrophilic lung inflammation after aerosolized LPS	Lung	[71]
RORα	Staggerer	Increased IL-1β, IL-6, & MIP-2 after LPS	Lung	[72]