TY - JOUR
T1 - Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes
AU - Jakubzick, Claudia
AU - Gautier, Emmanuel L.
AU - Gibbings, Sophie L.
AU - Sojka, Dorothy K.
AU - Schlitzer, Andreas
AU - Johnson, Theodore E.
AU - Ivanov, Stoyan
AU - Duan, Qiaonan
AU - Bala, Shashi
AU - Condon, Tracy
AU - vanRooijen, Nico
AU - Grainger, John R.
AU - Belkaid, Yasmine
AU - Ma'ayan, Avi
AU - Riches, David W.H.
AU - Yokoyama, Wayne M.
AU - Ginhoux, Florent
AU - Henson, Peter M.
AU - Randolph, Gwendalyn J.
N1 - Funding Information:
We thank C. Benoist and the Immunological Genome Consortium (Immgen) for their roles in the gene expression analysis. We thank J. Faith and J. Gordon for gnotobiotic mice, R. Schreiber for anti-IFN-γ mAb H22, L. Yang for technical assistance and advice with parabiosis, and D. Homann for assistance and reagents used in chemokine staining. This work was supported by National Institutes of Health grant AI049653 to G.J.R. with a Primary Caregiver’s Supplement to C.J. C.J. and P.M.H. were supported by NHLBI-HL81151 and NHLBI-HL115334. D.W.H.R. and T.C. were supported by the U.S. Department of Defense grant DOD W81XWH-07-1-0550-Mason. E.L.G. was funded in part by the AHA (10POST4160140). D.K.S. is supported by Training in Cancer Biology grant T32CA009547. A.S. and F.G. were supported by a Singapore Immunology Network core grant. The Immunological Genome project is funded by R24 AI072073 to C. Benoist. Funding related to the use of gnotobiotic mice was through Washington University Digestive Diseases Research Core Center (DDRCC) grant DK052574.
PY - 2013/9/19
Y1 - 2013/9/19
N2 - It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C+ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHCII), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.
AB - It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C+ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHCII), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.
UR - http://www.scopus.com/inward/record.url?scp=84884352076&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2013.08.007
DO - 10.1016/j.immuni.2013.08.007
M3 - Article
C2 - 24012416
AN - SCOPUS:84884352076
SN - 1074-7613
VL - 39
SP - 599
EP - 610
JO - Immunity
JF - Immunity
IS - 3
ER -