{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:48:06Z","timestamp":1791276486487,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The complement anaphylatoxin C5a is a critical mediator of allergic contact dermatitis, bridging essential aspects of innate and adaptive immunity. This anaphylatoxin functions by interacting with two 7-transmembrane segment receptors, the C5aR and C5L2. The C5aR is a classical G protein coupled receptor, whereas C5L2 is deficient in coupling to G proteins because of variations in the sequence. Our previous work in human neutrophils revealed a unique role for C5L2 in negatively modulating anaphylatoxin receptor mediated cellular activation through interactions with \u03b2-arrestin. When C5L2 is deficient, C5aR-mediated \u03b2-arrestin signaling is greatly enhanced. The work described in this study was undertaken first to determine the effect of C5L2 deficiency in a murine model of contact sensitivity, and second to determine whether the resultant exacerbation of inflammatory parameters reflects a negative modulatory function of C5L2 on the C5aR. First, we find dramatic increases in inflammation in C5L2\u2212\/\u2212 animals compared with wild type mice. Second, these increases are completely reversed following administration of mAb against the C5aR. Thus, in allergic contact sensitivity, as in isolated human neutrophils, C5L2 functions to suppress C5a-C5aR\u2013mediated responses, further underscoring its role as a negative regulator of anaphylatoxin activity.<\/jats:p>","DOI":"10.4049\/jimmunol.1301626","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T04:14:53Z","timestamp":1379391293000},"page":"4001-4009","source":"Crossref","is-referenced-by-count":37,"title":["Disruption of the Complement Anaphylatoxin Receptor C5L2 Exacerbates Inflammation in Allergic Contact Dermatitis"],"prefix":"10.1093","volume":"191","author":[{"given":"Ruobing","family":"Wang","sequence":"first","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Division of Respiratory Diseases, Department of Pediatrics, Children\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Lu","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Division of Respiratory Diseases, Department of Pediatrics, Children\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Gerard","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Division of Respiratory Diseases, Department of Pediatrics, Children\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma P","family":"Gerard","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Division of Respiratory Diseases, Department of Pediatrics, Children\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,15]]},"reference":[{"key":"2025032405482917100_r1","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1182\/blood-2008-04-151068","article-title":"Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis","volume":"112","author":"Lalli","year":"2008","journal-title":"Blood"},{"issue":"1","key":"2025032405482917100_r2","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.jaad.2003.01.002","article-title":"Contact dermatitis: a quarter century perspective","volume":"51","author":"Cohen","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"2025032405482917100_r3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.it.2004.06.003","article-title":"Extravascular T-cell recruitment requires initiation begun by Valpha14+ NKT cells and B-1 B cells","volume":"25","author":"Askenase","year":"2004","journal-title":"Trends Immunol."},{"key":"2025032405482917100_r4","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1084\/jem.20020649","article-title":"B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity","volume":"196","author":"Tsuji","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032405482917100_r5","first-page":"65","article-title":"Contact dermatitis I. Pathophysiology of contact sensitivity","volume":"9","author":"Krasteva","year":"1999","journal-title":"Eur. J. Dermatol."},{"key":"2025032405482917100_r6","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1084\/jem.186.7.1015","article-title":"Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon gamma: a possible initiating role of B cells","volume":"186","author":"Tsuji","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025032405482917100_r7","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.4049\/jimmunol.165.3.1588","article-title":"Early local generation of C5a initiates the elicitation of contact sensitivity by leading to early T cell recruitment","volume":"165","author":"Tsuji","year":"2000","journal-title":"J. Immunol."},{"key":"2025032405482917100_r8","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.4049\/jimmunol.156.12.4644","article-title":"Possible involvement of C5\/C5a in the efferent and elicitation phases of contact sensitivity","volume":"156","author":"Tsuji","year":"1996","journal-title":"J. Immunol."},{"key":"2025032405482917100_r9","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1600-0625.2011.01295.x","article-title":"A protective role of complement component 3 in T cell-mediated skin inflammation","volume":"20","author":"Purwar","year":"2011","journal-title":"Exp. Dermatol."},{"key":"2025032405482917100_r10","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.4049\/jimmunol.177.6.3686","article-title":"Invariant NKT cells rapidly activated via immunization with diverse contact antigens collaborate in vitro with B-1 cells to initiate contact sensitivity","volume":"177","author":"Campos","year":"2006","journal-title":"J. Immunol."},{"key":"2025032405482917100_r11","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1124\/pr.111.005223","article-title":"International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors","volume":"65","author":"Klos","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"2025032405482917100_r12","doi-asserted-by":"crossref","first-page":"39677","DOI":"10.1074\/jbc.C500287200","article-title":"An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2","volume":"280","author":"Gerard","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025032405482917100_r13","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0161-5890(00)00067-5","article-title":"A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells","volume":"37","author":"Ohno","year":"2000","journal-title":"Mol. Immunol."},{"key":"2025032405482917100_r14","doi-asserted-by":"crossref","first-page":"9406","DOI":"10.1021\/bi034489v","article-title":"C5L2, a nonsignaling C5A binding protein","volume":"42","author":"Okinaga","year":"2003","journal-title":"Biochemistry"},{"key":"2025032405482917100_r15","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.molimm.2008.11.001","article-title":"The human complement fragment receptor, C5L2, is a recycling decoy receptor","volume":"46","author":"Scola","year":"2009","journal-title":"Mol. Immunol."},{"key":"2025032405482917100_r16","doi-asserted-by":"crossref","first-page":"7633","DOI":"10.1074\/jbc.M109.092106","article-title":"The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction","volume":"285","author":"Bamberg","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2025032405482917100_r17","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.4049\/jimmunol.0802830","article-title":"CD8 T cells producing IL-17 and IFN-gamma initiate the innate immune response required for responses to antigen skin challenge","volume":"182","author":"Kish","year":"2009","journal-title":"J. Immunol."},{"key":"2025032405482917100_r18","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1096\/fj.12-220509","article-title":"C5L2: a controversial receptor of complement anaphylatoxin, C5a","volume":"27","author":"Li","year":"2013","journal-title":"FASEB J."},{"key":"2025032405482917100_r19","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2353\/ajpath.2007.060573","article-title":"Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies","volume":"170","author":"Xiao","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2025032405482917100_r20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.imbio.2012.04.001","article-title":"C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice","volume":"218","author":"Fisette","year":"2013","journal-title":"Immunobiology"},{"key":"2025032405482917100_r21","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1096\/fj.04-3424fje","article-title":"Evidence for a functional role of the second C5a receptor C5L2","volume":"19","author":"Gao","year":"2005","journal-title":"FASEB J."},{"key":"2025032405482917100_r22","doi-asserted-by":"crossref","first-page":"C1731","DOI":"10.1152\/ajpcell.00213.2011","article-title":"Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway","volume":"302","author":"Cao","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025032405482917100_r23","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1126\/science.273.5282.1722","article-title":"Neurogenic amplification of immune complex inflammation","volume":"273","author":"Bozic","year":"1996","journal-title":"Science"},{"key":"2025032405482917100_r24","doi-asserted-by":"crossref","first-page":"510","DOI":"10.4049\/jimmunol.180.1.510","article-title":"Multichannel fluorescence spinning disk microscopy reveals early endogenous CD4 T cell recruitment in contact sensitivity via complement","volume":"180","author":"Norman","year":"2008","journal-title":"J. Immunol."},{"key":"2025032405482917100_r25","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1189\/jlb.0304193","article-title":"The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites","volume":"76","author":"Engeman","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"2025032405482917100_r26","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.4049\/jimmunol.0901767","article-title":"IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes","volume":"184","author":"Pennino","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405482917100_r27","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/ni.1926","article-title":"Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma","volume":"11","author":"Lajoie","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032405482917100_r28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nm1753","article-title":"Functional roles for C5a receptors in sepsis","volume":"14","author":"Rittirsch","year":"2008","journal-title":"Nat. Med."},{"key":"2025032405482917100_r29","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1084\/jem.20041967","article-title":"Decay-accelerating factor modulates induction of T cell immunity","volume":"201","author":"Heeger","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032405482917100_r30","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.immuni.2008.02.001","article-title":"Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells","volume":"28","author":"Strainic","year":"2008","journal-title":"Immunity"},{"key":"2025032405482917100_r31","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1172\/JCI61019","article-title":"Antigen-presenting cell-derived complement modulates graft-versus-host disease","volume":"122","author":"Kwan","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2025032405482917100_r32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1600-0625.2011.01403.x","article-title":"Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2 mediated allergic contact dermatitis","volume":"21","author":"Niebuhr","year":"2012","journal-title":"Exp. Dermatol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/8\/4001\/62513748\/1301626.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/8\/4001\/62513748\/1301626.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T07:14:22Z","timestamp":1742886862000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/8\/4001\/7966665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1301626","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,10]]},"published":{"date-parts":[[2013,10]]}}}